Biology subjects

Wright, B.

Publications and source records attributed to Wright, B..

8 recordsLinked to original sources

bioRxiv2026

Operationalising LLM-assisted screening of literature to support systematic reviews

Large language models (LLMs) can ease the work of screening titles and abstracts for systematic reviews, but obtaining reliable results requires researchers to make practical choices about which LLMs to use, how to combine their scores into a ranking, and how far down that ranking to read. We aimed to identify a general- purpose workflow that screens accurately, minimises human review effort, and generalises across environmental literature corpora. We ran an ensemble of five open-source LLMs across ten human-annotated systematic reviews from the field of ecology and environmental science spanning 19,155 studies. We then asked: (1) how well an ensemble of LLMs ranks relevant papers above irrelevant ones, and (2) where a human reviewer should stop working down that ranked list. A four-LLM ensemble chosen without any labels came close, on every review, to the best ranking achievable with that review's annotations (mean Average Precision 0.66 versus 0.68). We tested different rules for when to stop human review, finding that a single SAFE stopping rule chosen in advance recovered greater than 95% of relevant records on all ten reviews while requiring a human to screen 56% of the corpus on average. Against the established open-source active-learning tool ASReview, this label-free ranking reached the same recall target at lower human workload on seven of the ten reviews (39% versus 42% of the corpus on average). The paper offers a complete workflow that can be adopted for new, unlabelled reviews, using open-source LLMs small enough to run on a high-end consumer laptop, and we provide it as an open-source R package.

ecology↗

bioRxiv2026

Dynamic diffusion analysis of the yeast plasma membrane using Airyscan based microscopic techniques

The yeast plasma membrane (PM) is highly compartmentalised into distinct nanoscale domains. The mechanisms by which this organisation regulates surface proteins are not fully understood, and it remains unclear how different biophysical modalities capture diffusion kinetics across varying spatial scales. Using confocal microscopy and an Airyscan2 detector, we benchmarked two prominent techniques: Fluorescence Correlation Spectroscopy (FCS) via the Zeiss Dynamics Profiler and Fluorescence Recovery After Photobleaching (FRAP). We quantified the lateral diffusion of three functionally diverse GFP-tagged model proteins: the exocytic t-SNARE Sso2, the lipid-binding protein Pmp3, and the eisosome-associated protein Ycp4. While diffusion coefficients aligned tightly between both modalities for Pmp3 and Ycp4, Sso2 exhibited a stark 14-fold discrepancy, displaying drastically faster local mobility by FCS compared to macroscopic recovery by FRAP. High-resolution 3D Structured Illumination Microscopy (3D-SIM) shows that Sso2 is partitioned into regional subdomains, that occupy less PM area than the network-like localisation of Pmp3. Our findings suggest that FCS captures rapid, localised diffusion within these microenvironments, whereas FRAP measures highly restricted transit across domain boundaries. Ultimately, this work demonstrates that membrane diffusion coefficients cannot be interpreted in isolation and capturing true lateral mobility requires pairing kinetic measurements with super-resolution spatial mapping to decode complex membrane compartmentalisation.

cell biology↗

bioRxiv2026

Orca vowels and consonants: convergent spectral structures across cetacean and human speech

The vocal communication system of orcas (Orcinus orca) has so far been analyzed primarily in terms of the fundamental frequency (F0) modulations, i.e. the frequency of their phonic lips vibration. The calls have been divided into clicks, pulsed calls, whistles and types thereof. By analyzing 61 hours of on-orca acoustic recordings and controlling for the effect of high-frequency components (HFC) and F0, we report structured formant patterns in orca vocalizations including diphthongal trajectories. Broadband spectrogram analysis reveals previously unreported formant patterns that appear independent of F0 and HFC and are hypothesized to result from air sac resonances. This study builds on the recent report of formant structure in vowel- and diphthong-like calls in another cetacean, sperm whales (Physeter macrocephalus). Using linguistic techniques, we further demonstrate that some calls are reminiscent of human consonant-vowel sequences, featuring bursts or abrupt decreases in amplitude. We also show that individual sparsely distributed clicks gradually transition into high frequency tonal calls, which aligns with analysis of sperm whale codas as vocalic pulses. The paper makes methodological contributions to the cetacean communication research by analyzing orca vocalizations with both narrowband and broadband spectrograms. The reported patterns are hypothesized to be actively controlled by whales and may carry communicative information. The spectral patterns shown in this study provide an added dimension to the orca communication system that merits further analysis and demonstrates convergent evolutions of similar phonological features in cetaceans (orca and sperm whale) and human communication systems.

animal behavior and cognition↗

bioRxiv2022

Antigen-dependent inducible T cell reporter system for PET imaging of breast cancer and glioblastoma

For the past several decades, chimeric antigen receptor T cell (CAR T) therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Using synthetic biology, we engineered T cells with a chimeric receptor SyNthetic Intramembrane Proteolysis Receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette upon recognition of specific tumor markers. We then applied a SNIPR-based positron emission tomography (PET) reporter system to two cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors respectively. Antigen-specific reporter induction of the SNIPR-PET T cells was confirmed in vitro using GFP fluorescence, luciferase luminescence, and the HSV-TK PET reporter with [18F]FHBG. T cells associated with their target antigens were successfully imaged using PET in dual xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII-animal models, with > 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. The main innovation described is therefore PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.

synthetic biology↗

bioRxiv2021

Ly6Chi monocytes are metabolically reprogrammed in the blood during inflammatory stimulation allowing for macrophage lineage commitment

Acute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a co-ordinated and precise manner. Using cell tracking, linage tracing and single cell transcriptomics we investigated the origin and transcriptional reprogramming of monocytes and macrophages in acute inflammation. Monocyte trafficking and adoptive transfer experiments revealed that monocytes undergo rapid phenotypic change as they exit the blood and give rise to monocyte-derived macrophages that persist during the resolution of inflammation. Single cell transcriptomics revealed significant heterogeneity within the surface marker defined CD11b+Ly6G-Ly6Chi monocyte population within the blood and at the site of inflammation. Lineage trajectory analysis revealed that Ly6Chi monocytes in the blood are re-programmed into a defined differentiation pathway following inflammatory stimulus. We show that two major transcriptional reprogramming events occur during the initial 6 h of Ly6Chi monocyte mobilisation, one in the blood priming monocytes for migration and a second at the site of inflammation. Pathway analysis revealed an important role for oxidative phosphorylation (OxPhos) during both these reprogramming events in a subset of M2-like cells. Experimentally we also demonstrate that OxPhos is essential for murine and human monocyte chemotaxis. These new findings opening up the possibility that altering monocyte metabolic capacity towards OxPhos could facilitate enhanced macrophage M2-like polarisation to aid inflammation resolution and tissue repair.

immunology↗

bioRxiv2019

The impact of leishmaniasis on mental health and psychosocial well-being: A systematic review

BackgroundLeishmaniasis is a neglected tropical parasitic disease endemic in South Asia, East Africa, South America and the Middle East. It is associated with low socioeconomic status (SES) and responsible for considerable mortality and morbidity. Reports suggest that patients with leishmaniasis may have a higher risk of mental illness (MI), psychosocial morbidity (PM) and reduced quality of life (QoL), but this is not well characterised. The aim of this study was to conduct a systematic review to assess the reported impact of leishmaniasis on mental health and psychosocial wellbeing.\n\nMethodsA systematic review of the literature was carried out. Pre-specified criteria were applied to identify publications including observational quantitative studies or systematic reviews. Two reviewers screened all of the titles, abstracts and full-studies and a third reviewer was consulted for disagreements. Data was extracted from papers meeting the criteria and quality appraisal of the methods was performed using the Newcastle-Ottowa Scale or the Risk of Bias in Systematic Review tool.\n\nResultsA total of 14 studies were identified from 12,517 records. Nine cross-sectional, three case-control, one cohort study and one systematic review were included. Eleven assessed MI outcomes and were measured with tools specifically designed for this; nine measured PM and 12 measured QoL using validated measurement tools. Quality appraisal of the studies showed that six were of good quality. Cutaneous leishmaniasis and post kala-azar dermal leishmaniasis showed evidence of associated MI and PM including depression, anxiety and stigma, while all forms of disease showed decreased QoL. The findings were used to inform a proposed model and conceptual framework to show the possible links between leishmaniasis and mental health outcomes.\n\nConclusionThere is evidence that leishmaniasis has an impact on MI, PM or QoL of patients and their families and this occurs in all the main subtypes of the disease. There are however large gaps in the evidence. Further research is required to understand the full extent of this problem and its mechanistic basis.\n\nAUTHOR SUMMARYLeishmaniasis is a parasitic disease prevalent in many low-and middle-income countries worldwide. In this study the authors looked for evidence as to whether leishmaniasis affected the mental health and quality of life of patients. To conduct the review, a wide search of the literature was conducted, where a total of 14 full articles were included and analysed. It was found that different forms of leishmaniasis (visceral leishmaniasis, cutaneous leishmaniasis and post kala-azar dermal leishmaniasis) do cause a significant impact on patients mental health and quality of life through societal factors such as stigma, lack of knowledge, culture and low self-esteem among others. However, no evidence of biological mechanisms was found linking leishmaniasis to mental illness or decreased quality of life. Despite being a very incapacitating disease physically, leishmaniasis also leads to mental illness and decreased quality of life, and should therefore be a priority on the global health agenda for both researchers and policy makers.

epidemiology↗

bioRxiv2019

Saxitoxin and tetrodotoxin bioavailability increases in future oceans

Increasing atmospheric levels of carbon dioxide are largely absorbed by the worlds oceans, decreasing surface water pH1. In combination with increasing ocean temperatures, these changes have been identified as a major sustainability threat to future marine life2. Interactions between marine organisms are known to depend on biomolecules, but the influence of oceanic pH on their bioavailability and functionality remains unexplored. Here we show that global change significantly impacts two ecological keystone molecules3 in the ocean, the paralytic toxins saxitoxin (STX) and tetrodotoxin (TTX). Increasing temperatures and declining pH increase the abundance of the toxic forms of these two neurotoxins in the water. Our geospatial global model highlights where this increased toxicity could intensify the devastating impact of harmful algal blooms on ecosystems in the future, for example through an increased incidence of paralytic shellfish poisoning (PSP). We also use these results to calculate future saxitoxin toxicity levels in Alaskan clams, Saxidomus gigantea, showing critical exceedance of limits save for consumption. Our findings for TTX and STX exemplarily highlight potential consequences of changing pH and temperature on chemicals dissolved in the sea. This reveals major implications not only for ecotoxicology, but also for chemical signals mediating species interactions such as foraging, reproduction, or predation in the ocean with unexplored consequences for ecosystem stability and ecosystem services.

pharmacology and toxicology↗

bioRxiv2018

BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors

Heterozygous germline mutations in BRCA2 predispose to breast and ovarian cancer. Contrary to non-cancerous cells, where BRCA2 deletion causes cell cycle arrest or cell death, BRCA2 inactivation in tumors is associated with uncontrolled cell proliferation. We set out to investigate this conundrum by exploring modalities of cell adaptation to loss of BRCA2 and focused on genome-wide transcriptome alterations. Human cells in which BRCA2 expression was inhibited using a doxycycline (DOX)-inducible shRNA for 4 or 28 days were subjected to RNA-seq analyses. Gene sets differentially expressed in BRCA2-deficient versus -proficient cells revealed a biphasic response to BRCA2 abrogation. The early, acute response consisted of downregulation of genes involved in cell cycle progression, DNA replication and repair and was associated with cell cycle arrest in G1. Surprisingly, the late, chronic response consisted predominantly of upregulation of innate immune response genes controlled by interferon. Activation of the cGAS-STING pathway detected in these cells further substantiated the concept that long-term BRCA2 abrogation triggers cell-intrinsic immune signaling. Importantly, we found that treatment with PARP inhibitors stimulated the interferon response in cells and tumors lacking BRCA2. We propose that PARP inhibitors may suppress growth of BRCA2-deficient cells and tumors, in part, by activating interferon signaling.

cancer biology↗