Biology subjects

Fuller, B.

Publications and source records attributed to Fuller, B..

3 recordsLinked to original sources

bioRxiv2024

When Rivals Are Absent: Male Aggression Towards Females in Bluefin Killifish

The process of obtaining mates, mating, and (potentially) caring for offspring is costly. While there are inherent costs to reproduction, behavioral interactions among individuals are often the primary drivers of reproductive costs. Males frequently compete for territories and females; females may compete for food or males; males often harass females. Here, we sought to determine whether reproductive costs were primarily due to male/male competition, female/female competition, or male/female interactions in the bluefin killifish. In this species, males guard small spawning territories where females visit them daily to spawn. To manipulate the potential for male and female competition and male/female interactions, we altered the sex ratio and density of each sex across four treatments (1 male: 1 female, 1 male : 3 females, 3 males: 1 female, 3 males: 3 females). Female mortality was higher than male mortality. Surprisingly, female mortality and male aggressive behaviors towards females (i.e., chases) were highest in treatments with a single male. Male-male aggression was present, but males often resolved these disputes via signaling by flaring their fins. There was little evidence for overt aggression among females. When males lack rivals, they turn their territorial defense towards females. These costs help explain why, in nature, females promptly leave male territories following spawning and join loose shoals with conspecific females and minnows.

animal behavior and cognition↗

bioRxiv2021

Nanopore sequencing methods detect cell-free DNA associated with minimal residual disease and central nervous system infiltration in pediatric Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL) patients that are positive for minimal residual disease (MRD) after therapy or have leukemic infiltration into the central nervous system (CNS) are considered high risk and receive intensive chemotherapy regimens. Current methods to diagnose MRD and CNS infiltration rely on detecting leukemic cells in patient samples using pathology, flow cytometry, or next-generation sequencing. However, leukemic blasts may persist in the patient but not be physically present in bone marrow biopsy or biofluid sample, leading to inaccurate or delayed patient diagnosis. We have developed a nanopore sequencing workflow to detect B-ALL-associated cell-free DNA (cfDNA) in blood and cerebrospinal fluid (CSF) samples. Quantitation of B-cell specific VDJ recombination events in cfDNA samples defined B-ALL clonal heterogeneity. This workflow allowed us to track the response of individual B-ALL clones throughout treatment. Detection of cfDNA also predicted the clinical diagnosis of MRD and CNS disease. Importantly, we identified patients diagnosed as CNS negative who had low B-cell derived cell-free DNA levels in their CSF sample that correlated with B-cell clones present in the bone marrow. These data suggest that cfDNA assays may be useful in detecting the presence of ALL in the patient even when blasts are not in the biofluid sample. Nanopore analysis of cell-free DNA is a simple, rapid, and inexpensive assay that can serve as a valuable complement to traditional clinical diagnostic approaches for ALL. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=50 SRC="FIGDIR/small/462067v2_ufig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@1373bd3org.highwire.dtl.DTLVardef@138b2e3org.highwire.dtl.DTLVardef@168661forg.highwire.dtl.DTLVardef@1088626_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2020

Negative durotaxis: cell movement toward softer environments

Durotaxis - the ability of cells to sense and migrate along stiffness gradients - is important for embryonic development and has been implicated in pathologies including fibrosis and cancer. Although cellular processes can sometimes turn toward softer environments, durotaxis at the level of cells has thus far been observed exclusively as migration from soft to stiff regions. The molecular basis of durotaxis, especially the factors that contribute to different durotactic behaviors in various cell types, are still inadequately understood. With the recent discovery of optimal stiffness, where cells generate maximal traction forces on substrates in an intermediate stiffness range, we hypothesized that some migratory cells may be capable of moving away from stiff environments and toward matrix on which they can generate more traction. Combining hydrogel-based stiffness gradients, live-cell imaging, genetic manipulations, and computational modeling, we found that cells move preferentially toward their stiffness optimum for maximal force transmission. Importantly, we directly observed biased migration toward softer environments, i.e. negative durotaxis, in human glioblastoma cells. This directional migration did not coincide with changes in FAK, ERK or YAP signaling, or with altered actomyosin contractility. Instead, integrin-mediated adhesion and motor-clutch dynamics alone are sufficient to generate asymmetric traction to drive both positive and negative durotaxis. We verified this mechanistically by applying a motor-clutch-based model to explain negative durotaxis in the glioblastoma cells and in neurites, and experimentally by switching breast cancer cells from positive to negative durotaxis via talin downregulation. Our results identify the likely molecular mechanisms of durotaxis, with a cells contractile and adhesive machinery dictating its capacity to exert traction on mechanically distinct substrates, directing cell migration.

biophysics↗