Biology subjects

Thornton, L.

Publications and source records attributed to Thornton, L..

5 recordsLinked to original sources

bioRxiv2026

High Connectivity, Local Signatures: Genomic and Otolith Evidence from Reef-Associated Snappers.

Connectivity in reef-associated fishes emerges from processes operating across multiple spatial and temporal scales, yet these processes are rarely evaluated jointly. Here, we integrated genome-wide single-nucleotide polymorphisms (SNPs) data and otolith elemental signatures to examine connectivity in Red Snapper (Lutjanus campechanus) and Vermilion Snapper (Rhomboplites aurorubens) across 14 reefs and banks from the Flower Garden Banks National Marine Sanctuary and neighboring banks to the east. We tested whether genomic variation revealed population structure across geographic and depth gradients (shallow, upper mesophotic, and lower mesophotic), whether otolith chemistry captured fine-scale site-specific patterns of environmental exposure and habitat use not resolved by genetic markers alone, and how these complementary signals related to spatial variation in age structure and growth dynamics. Genome-wide SNP data revealed little detectable spatial genetic structure across the sampled banks in either species. In contrast, otolith microchemistry revealed pronounced site-associated environmental structuring, indicating that individuals experience localized habitat conditions within a regionally connected system. Red Snapper exhibited otolith signatures consistent with reef-associated environments, whereas Vermilion Snapper showed more variable elemental signatures, indicating exposure to a broader or more heterogeneous range of habitats. Spatial variation in age structure and growth provided additional demographic context, indicating that local differences among banks can emerge despite weak genomic differentiation. Together, these results show that fine-scale ecological and demographic differentiation can exist within a genetically connected system and that otolith chemistry provides critical information on post-settlement processes at scales not captured by genetic markers alone. By linking regional genomic connectivity with otolith-derived habitat signatures and demographic variation, this integrative framework provides a more comprehensive basis for understanding resilience and informing fisheries management in shelf-edge reef systems.

ecology↗

bioRxiv2025

Dynamic BH3 profiling predicts clinical outcomes in acute myeloid leukemia

Predictive biomarkers can potentially meet the need for improved drug assignment in acute myeloid leukemia (AML). Fewer than half of AML patients have actionable mutations: consequently, targeted therapy achieves remission in only a fraction of those who have them. Dynamic BH3 Profiling (DBP), a functional assay, can measure changes in ex vivo drug-induced apoptotic priming in multiple cancers. To assess the feasibility and predictive capacity of DBP in AML, we prospectively tested DBP using a fixed-drug panel in myeloblasts from 92 patients. We generated a database combining genetic and functional annotation. Established AML clinical and genetic prognostic characteristics were associated with drug-induced apoptotic priming. We observed distinct interpatient sensitivities to single drugs or combinations with the BCL2-inhibitor venetoclax, and intrapatient apoptotic priming differences based on CD123-expression within distinct cell subpopulations. DBP further predicted the likelihood of remission to chemotherapy and targeted agents, supporting its use to identify optimal personalized therapy. Statement of significanceDynamic BH3 profiling provides patient-specific drug vulnerability data in real-time to inform prognosis and therapy selection. Key takeawaysO_LIDynamic BH3 profiling can be performed on bone marrow and leukemic blood from AML patients in 48 hours. C_LIO_LIKnown clinical prognostic factors associate with drug-induced apoptotic priming in AML. C_LIO_LIDrug-induced apoptotic priming identifies drug vulnerabilities in individual patients and predicts clinical response to chemotherapy and small molecule inhibitors. C_LI

cancer biology↗

bioRxiv2025

Sialylated CD43 is a glyco-immune checkpoint for macrophage phagocytosis

Macrophages in the tumor microenvironment exert potent anti-tumorigenic activity through phagocytosis. Yet therapeutics that enhance macrophage phagocytosis have not improved outcomes in clinical trials for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). To systematically identify regulators of phagocytosis, we performed genome-scale CRISPR knockout screens in human leukemia cells co-cultured with human monocyte-derived macrophages. Surprisingly, we found that whereas the classic "dont eat me" signal CD47 inhibited mouse macrophages, it did not inhibit phagocytosis by human macrophages. In contrast, the O-linked glycosylation and sialylation pathways were strong negative regulators of phagocytosis. In AML, the cell surface O-linked glycoprotein CD43 was the major effector of the O-linked glycosylation and sialylation pathways. Genetic deletion or antibody blockade of CD43 enhanced macrophage phagocytosis. This work highlights the importance of using human platforms to identify immune checkpoints, and nominates CD43 as a glyco-immune regulator of human macrophage phagocytosis.

cancer biology↗

bioRxiv2024

Unlocking the secrets of kangaroo locomotor energetics: Postural adaptations underpin increased tendon stress in hopping kangaroos

Hopping kangaroos exhibit remarkably little change in their rate of metabolic energy expenditure with locomotor speed compared to other running animals. This phenomenon may be related to greater elastic energy savings due to increasing tendon stress; however, the mechanisms which enable the rise in stress without additional muscle work remain poorly understood. In this study, we created a three-dimensional (3D) kangaroo musculoskeletal model, integrating 3D motion capture and force plate data, to analyse the kinematics and kinetics of hopping red and grey kangaroos. Using our model, we evaluated how body mass and speed influence (i) hindlimb posture, (ii) effective mechanical advantage (EMA), (iii) the associated tendon stress in the ankle extensors, and (iv) ankle work during hopping. We found that increasing ankle dorsiflexion and metatarsophalangeal plantarflexion likely played an important role in decreasing ankle EMA by altering both the muscle and external moment arms, which subsequently increased energy absorption and peak tendon stress at the ankle. Surprisingly, kangaroo hindlimb posture changes appeared to contribute to increased tendon stress, allowing more elastic energy storage at faster speeds. These posture-mediated increases in elastic energy storage and return could be a key factor enabling kangaroos to achieve energetic benefits at faster hopping speeds, but may limit the performance of large kangaroos due to the risk of tendon rupture.

zoology↗

bioRxiv2021

Non-coding function for mRNAs in Focal Adhesion Architecture and Mechanotransduction

Messenger RNA (mRNA) compartmentalization within the cytosol is well-recognized as a key mechanism of local translation-mediated regulation of protein levels, but whether such localization could be a means of exercising non-coding mRNA function is unknown. Here, we explore non-coding functions for mRNAs associated with focal adhesions (FAs), cellular structures responsible for mediating cell adhesion and response to changes in the extracellular matrix (ECM). Using high-throughput single molecule imaging and genomic profiling approaches, we find that mRNAs with distinct sequence characteristics localize to FAs in different human cell types. Notably, [~]85% of FA-mRNAs are not translationally active at steady state or under conditions of FA dissolution or activation. Untranslated mRNA sequences are anchored to FA based on their functional states by the RNA binding protein, G3BP1, forming biomolecular granules. Removing RNA or G3BP1, but not blocking new polypeptide synthesis, dramatically changes FA protein composition and organization, resulting in loss of cell contractility and cellular ability to adapt to changing ECM. We have therefor uncovered a novel, non-coding role for mRNAs as scaffolds to maintain FA structure and function, broadening our understating of noncanonical mRNA functions.

cell biology↗