Biology subjects

Smith, A. A.

Publications and source records attributed to Smith, A. A..

9 recordsLinked to original sources

bioRxiv2026

Protection against disseminated disease following reinfection with Mycobacterium tuberculosis requires CD8+ lymphocytes

Concomitant immunity is protective adaptive immunity conferred by pre-existing infection against subsequent exposures. This phenomenon is effective in the context of human tuberculosis (TB) and has been successfully recapitulated in non-human primates (NHPs). We previously demonstrated that depletion of CD4 T cells prior to secondary challenge with Mycobacterium tuberculosis (Mtb) only partially abrogated protection, implicating a critical role for additional cell types. Here, we describe the effects of depleting CD8 expressing cells in this model. CD4+ T cells in the airway were unable to compensate for lost cytotoxicity due to CD8 depletion. Contrary to the results of CD4 depletion, CD8 depleted animals exhibited a unique inability to limit Mtb dissemination, with significant lymph node involvement despite a short 4-week infection. These data suggest that concomitant immunity relies on non-redundant roles played by CD8+ lymphocytes. Thus, future vaccines should be designed to induce effective responses by both CD4+ and CD8+ populations to maximize efficacy.

immunology↗

bioRxiv2026

Using a GPT-5-driven autonomous lab to optimize the cost and titer of cell-free protein synthesis

We used an autonomous lab, comprising a large language model (LLM) and a fully automated cloud laboratory, to optimize the cost efficiency of cell-free protein synthesis (CFPS). By conducting iterative optimization, the LLM-driven autonomous lab was able to achieve a 40% reduction in the specific cost ($/g protein) of CFPS relative to the state of the art (SOTA). This cost reduction was accompanied by a 27% increase in protein production titer (g/L). Iterative experimental design, experiment execution, data capture and analysis, data interpretation, and new hypothesis generation were all handled by the LLM-driven autonomous lab. The interface between OpenAIs GPT-5 LLM and Ginkgo Bioworks cloud laboratory incorporated built-in validation checks via a Pydantic schema to ensure that AI-designed experiments were properly specified. Experimental designs were translated into programmatic specification of multi-instrument biological workflows by Ginkgos Catalyst software and executed on Ginkgos Reconfigurable Automation Cart (RAC) laboratory automation platform, with human intervention largely limited to reagent and consumables preparation, loading and unloading. By integrating LLMs with programmatic control of a cloud lab, we demonstrate that an LLM-driven autonomous lab can successfully perform a real-world scientific task, highlighting the potential of AI-driven autonomous labs for scientific advancement.

synthetic biology↗

bioRxiv2025

Claws that snap: the raptorial mechanism of dryinid wasps

Prey capture is a key selection pressure, often favoring extreme performance morphologies. Many mechanisms of prey capture, however, remain poorly understood. In this study, we document the remarkable raptorial behavior and evolutionary biomechanics of the "pincer wasps" (Hymenoptera: Dryinidae). Dryinid claws, previously thought to function as simple vises (Nachtigall-&-Nachtigall-1974), are shown to possess "snap traps", or claws that close rapidly upon prey contact. Detailed morphological analysis, using synchrotron-radiation microtomography (SR-{micro}-CT), reveals that all long-clawed dryinids can overcenter their specialized anterior pretarsal claws, presumably allowing elastic energy storage in the pretarsal apodemes. Uniquely, explosive release of this energy, leading to claw closure, appears to occur not through active withdrawal of a latch, but as the direct consequence of contact with the prey: impact hyperextends a specialized trigger-joint complex of the tarsus, pulling the claw back into undercenter alignment, and so freeing the stretched apodeme to fully recoil. Such a "contact trigger" is eminently useful, as these trap-claw wasps prey on insects with explosive jump capacity; by linking trap shutting with prey contact, success chances are increased. Paleontological and allometric analyses suggest that the raptorial behavior likely preceded the evolution of overcentering, which appears to have evolved via release from developmental constraint on anteroposterior symmetry, leading to a distinct scaling rule. These findings expand the documented diversity of spring-loaded biological mechanisms and establish Dryinidae as a promising system for studying how developmental constraints, mechanical demands, and functional innovation shape ecomorphological diversity. HIGHLIGHTSO_LIDryinidae catch prey with spring-loaded trap claws, relying on a unique direct-action trigger. C_LIO_LIRaptorial behavior evolved first, followed by the functional derivation of two separate components. C_LIO_LIThe evolution of novel raptorial mechanism was enabled by release of ancestral developmental constraint. C_LI

evolutionary biology↗

bioRxiv2025

Natural history museums are missing an opportunity to present research and collections on YouTube

There have been repeated calls in the US for scientists to communicate the importance of biological collections to both a general public audience and to policy makers. Natural history museums that house both collections and research staff while maintaining online media presences, are well positioned to communicate that value. Our study aims to understand how these museums present themselves and their research and collections via YouTube. We created a standardized and repeatable 15-question codebook to categorize content and production choices in museum account YouTube posts. In total, we analyzed 437 videos posted by 28 natural history museums in the US in 2019 and 2023, showing that messages featuring museum science are uncommon. Instead, YouTube users are likely to encounter live event recordings or promotional content related to museum or exhibit information. Research and collections themed content represents an opportunity gap for museums to engage YouTube audiences in science. If natural history museums that maintain both collections and research staff want to answer the repeated calls of communicating the importance of collections in research, then we recommend either (1) incorporating research and collections into their other video types, and/or (2) looking to other YouTube channels, some of which are subsidiary to museum institutional accounts, as a model for research and collections content strategies.

scientific communication and education↗

bioRxiv2024

A diverse landscape of FGFR alterations and co-mutations defines novel therapeutic strategies in pediatric low-grade gliomas

Alterations in Fibroblast growth factor receptor (FGFR)-family proteins frequently occur as oncogenes in many cancers, including a subset of pediatric gliomas. Here, we performed a genomic analysis of 11,635 gliomas across ages and found that 4.5% of all gliomas harbor FGFR alterations including structural variants (SV) and single nucleotide variants (SNV), with an incidence of almost 10% in pediatric gliomas. FGFR family members are differentially enriched by age, tumor grade, and histological subtype, with FGFR1-alterations associated with glioneuronal histologies and pediatric low-grade gliomas. Across development, we find FGFR1 expression in both neuronal and glial precursors, while FGFR3 expression is largely restricted to astrocytic lineages. Leveraging novel isogenic model systems, we confirm FGFR1 alterations to be sufficient to activate MAPK and mTOR signaling, drive gliomagenesis, activate neuronal transcriptional programs and exhibit sensitivity to MAPK pathway inhibitors, including pan-FGFR inhibitors. Models driven by FGFR1 SVs exhibited different patterns of sensitivity compared to those driven by SNVs. Finally, we performed a retrospective analysis of clinical responses in children diagnosed with FGFR-driven gliomas and found that targeted MAPK or FGFR-inhibition with currently available inhibitors is largely associated with stability of disease. This study provides key insights into the biology of FGFR1-altered gliomas, therapeutic strategies to target them and associated challenges that still need to be overcome.

cancer biology↗

bioRxiv2023

A "suicide" BCG strain provides enhanced immunogenicity and robust protection against Mycobacterium tuberculosis in macaques

Intravenous (IV) BCG delivery provides robust protection against Mycobacterium tuberculosis (Mtb) in macaques but poses safety challenges. Here, we constructed two BCG strains (BCG-TetON-DL and BCG-TetOFF-DL) in which tetracyclines regulate two phage lysin operons. Once the lysins are expressed, these strains are killed in immunocompetent and immunocompromised mice yet induced similar immune responses and provided similar protection against Mtb challenge as wild type BCG. Lysin induction resulted in release of intracellular BCG antigens and enhanced cytokine production by macrophages. In macaques, cessation of doxycycline administration resulted in rapid elimination of BCG-TetOFF-DL. However, IV BCG-TetOFF-DL induced increased pulmonary CD4 T cell responses compared to WT BCG and provided robust protection against Mtb challenge, with sterilizing immunity in 6 of 8 macaques, compared to 2 of 8 macaques immunized with WT BCG. Thus, a "suicide" BCG strain provides an additional measure of safety when delivered intravenously and robust protection against Mtb infection.

immunology↗

bioRxiv2022

Function and evolution of aquaporin IsAQP1 in the Lyme disease vector Ixodes scapularis

Ticks are important vectors of pathogenic viruses, bacteria, and protozoans to humans, wildlife, and domestic animals. Due to their life cycle, ticks face significant challenges related to water homeostasis. When blood-feeding they must excrete water and ions, but when off-host (for stretches lasting several months) they must conserve water to avoid desiccation. Aquaporins (AQPs), a family of membrane-bound water channels, are key players in osmoregulation in many animals but remain poorly characterized in ticks. Here, we bioinformatically identified AQP-like genes from the deer tick Ixodes scapularis and used phylogenetic approaches to map the evolution of the aquaporin gene family in arthropods. We find that most arachnid AQP-like sequences (including those of I. scapularis) form a monophyletic group clustered within aquaglycerolporins (GLPs) from bacteria to vertebrates. This gene family is absent from insects, revealing divergent evolutionary paths for AQPs in different hematophagous arthropods. We next sequenced the full-length cDNA of I. scapularis aquaporin 1 (IsAQP1) and expressed it heterologously in Xenopus oocytes to functionally characterize its permeability to water and solutes. We additionally examined IsAQP1 expression across different life stages and adult female tissues. We found IsAQP1 to be an efficient water channel with salivary gland-specific expression, implying its function may be closely tied to osmoregulation during blood-feeding. Its functional properties were unique: unlike most GLPs, IsAQP1 has low glycerol permeability, and unlike most AQPs, it is insensitive to mercury. Together, our results suggest IsAQP1 plays an important role in tick water balance during blood feeding and may hold promise as a target for novel vector control efforts. Graphical TOC/Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY eTOCIsAQP1, an aquaporin found in the black legged tick (Ixodes scapularis), is a functional water channel with low permeability to glycerol. In a phylogenetic analysis of 176 sequences from 48 arachnid species, most tick and other arachnid AQP-like genes formed a monophyletic clade nested within aquaglyceroporins (GLPs). IsAQP1 shows salivary-gland specific expression in adult females--with highest expression in unfed females--suggesting a role in water balance during blood feeding.

genetics↗

bioRxiv2021

A Novel Power-Amplified Jumping Behavior in Larval Beetles (Coleoptera: Laemophloeidae)

Larval insects use many methods for locomotion. Here we describe a previously unknown jumping behavior in a group of beetle larvae (Coleoptera: Laemophloeidae). We analyze and describe this behavior in Laemophloeus biguttatus and provide information on similar observations for another laemophloeid species, Placonotus testaceus. Laemophloeus biguttatus larvae prelude jumps by arching their body while gripping the substrate with their legs over a period of 0.22 {+/-} 0.17s. This is followed by a rapid ventral curling of the body after the larvae releases its grip that launches them into the air. Larvae reached takeoff velocities of 0.47 {+/-} 0.15 m s-1 and traveled 11.2 {+/-} 2.8 mm (1.98 {+/-} 0.8 body lengths) horizontally and 7.9 {+/-} 4.3 mm (1.5 {+/-} 0.9 body lengths) vertically during their jumps. Conservative estimates of power output revealed that not all jumps can be explained by direct muscle power alone, suggesting Laemophloeus biguttatus uses a latch-mediated spring actuation mechanism (LaMSA) in which interaction between the larvaes legs and the substrate serves as the latch. MicroCT scans and SEM imaging of larvae did not reveal any notable modifications that would aid in jumping. Although more in-depth experiments could not be performed to test hypotheses on the function of these jumps, we posit that this behavior is used for rapid locomotion which is energetically more efficient than crawling the same distance to disperse from their ephemeral habitat. We also summarize and discuss jumping behaviors among insect larvae for additional context of this behavior in laemophloeid beetles.

animal behavior and cognition↗

bioRxiv2019

A semi-automated technique for adenoma quantification in the ApcMin mouse using FeatureCounter

Colorectal cancer is a major contributor to death and disease worldwide. The ApcMin mouse is a widely used model of intestinal neoplasia, as it carries a mutation also found in human colorectal cancers. However, the method most commonly used to quantify tumour burden in these mice is manual adenoma counting, which is time consuming and poorly suited to standardization across different laboratories. We describe a method to produce suitable photographs of the small intestine, process them with an ImageJ macro, FeatureCounter, which automatically locates image features potentially corresponding to adenomas, and a machine learning pipeline to identify and quantify them. Compared to a manual method, the specificity (or True Negative Rate, TNR) and sensitivity (or True Positive Rate, TPR) of this method in detecting adenomas are similarly high at about 80% and 87%, respectively. Importantly, total adenoma area measures derived from the automatically-called tumours were just as capable of distinguishing high-burden from low-burden mice as those established manually. Overall, our strategy is quicker, helps control experimenter bias and yields a greater wealth of information about each tumour, thus providing a convenient route to getting consistent and reliable results from a study.

cancer biology↗