Biology subjects

Gregory, R.

Publications and source records attributed to Gregory, R..

8 recordsLinked to original sources

bioRxiv2026

Exploring the use of state of nature metrics to screen global business operations for ecological sensitivity and to select priority sites for disclosure

Businesses are increasingly encouraged to disclose their nature-related dependencies, impacts, risks and opportunities. A common component of sustainability reporting is screening operational sites for ecologically sensitivity to identify locations for further evaluation and action. However, with 600+ biodiversity metrics available, selecting and interpreting appropriate metrics remains challenging for business. We developed a simple screening framework informed by the Taskforce for Nature-Related Financial Disclosures guidance, grouping eleven widely used global biodiversity metrics into four complementary [&prime]baskets[&prime], representing different aspects of biodiversity. We created hypothetical but realistic mining, onshore wind energy and agricultural companies, to assess how metric choice, buffer size, scoring approach and sensitivity thresholds influence screening outcomes. Our basket framework consistently identified similar high-priority sites across metric combinations, but site rankings varied with methodological choices. We recommend clearer guidance on metric selection and application, alongside greater transparency from business regarding assumptions, methods and limitations when screening sites for ecological sensitivity.

ecology↗

bioRxiv2026

Development of an ELISA-Based Pulldown Approach for Functional Analysis of Antigen-Specific Antibodies

The identification of antigen-specific neutralising antibodies is essential for vaccine development and therapeutic discovery, yet current methods either lack functional readouts or are impractical for polyclonal sera from large cohorts. Here, we describe an ELISA-based pulldown methodology that isolates functional antibodies from serum samples while preserving their neutralising activity for downstream applications. We optimised elution conditions using 3M MgCl2 in HEPES buffer, which effectively disrupts antibody-antigen interactions without dislodging immobilised antigen or impairing antibody function. The assay demonstrated 100% specificity and 77.78% sensitivity for detecting known positive samples. Compatibility with pseudotype neutralisation assays was established, with maximum tolerable MgCl2 concentrations defined for direct use without dialysis. As proof-of-concept, we applied the method to identify domain-specific neutralising antibodies against the influenza virus haemagglutinin, distinguishing head-targeting from stem-targeting responses in human sera. This methodology provides a scalable platform for dissecting functional antibody responses with epitope-level resolution. HighlightsO_LIAdapted ELISA pulldown isolates functional antigen-specific antibodies C_LIO_LI3M MgCl2 elution preserves antibody functionality C_LIO_LICompatible with Influenza pseudotype neutralisation assays C_LIO_LIAllows for the identification of region-specific antibodies C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/706726v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1ab9bforg.highwire.dtl.DTLVardef@98e20borg.highwire.dtl.DTLVardef@120687dorg.highwire.dtl.DTLVardef@abf267_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

RNA methylation controls stress granule formation and function during erythropoiesis

Stress granules (SGs) are crucial in RNA regulation, affecting cell fate and function. SGs contain RNAs, some of which can be methylated. We studied m6A RNA modifications during the human CD34+ HSPCs (hCD34+) differentiating into erythroid cells and found that mRNAs encoding many erythroid-specific proteins had decreased methylation during differentiation. Increased levels ALKBH5 demethylase during erythropoiesis controls the levels of the 3UTR methylation of these mRNAs. hCD34+ carrying ALKBH5 mutations demonstrated a block in erythropoiesis, and mass-spectrometry studies of the mutant cells showed decreased levels of SG proteins, including the core granule protein ATXN2. ALKBH5 directly regulates the methylation of the mRNA of ATXN2. ATXN2 overexpression accelerated the erythroid differentiation of HSPCs and rescued the erythroid differentiation of ALKBH5 mutant cells. Very few SGs are found in normal human erythroid progenitors. SGs accumulated substantially in ALKBH5 mutant cells, and surprisingly overexpression of ATNX2 reduced SG numbers to normal. Polysome analysis demonstrated m6A-modified RNAs to be enriched in the pre-polysome fractions that were less translated. This work establishes a mechanism by which during stress, ATXN2 facilitates the release of SG-stored m6A-modified RNAs including erythroid-specific and SG-enriched RNAs that are loaded onto functional ribosomes, allowing better translation and accelerated erythroid differentiation during stress.

cell biology↗

bioRxiv2022

Selenium Silk Nanostructured Films for Antifungal and Antibacterial Treatments

The rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. An orthogonal approach, therefore, is to explore biomaterials with physical modes of action which have the potential to generate antimicrobial activity and in some cases even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and non-cytotoxic towards mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a two-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials.

microbiology↗

bioRxiv2022

Overconfidence undermines global wildlife abundance trends

In the face of rapid global change and an uncertain fate for biodiversity, it is vital to quantify trends in wild populations. These trends are typically estimated from abundance time series for suites of species across large geographic and temporal scales. Such data implicitly contain phylogenetic, spatial, and temporal structure which, if not properly accounted for, may obscure the true magnitude and direction of biodiversity change. Here, using a novel statistical framework to simultaneously account for all three of these structures, we show that the majority of current abundance trends estimates among 10 high-profile datasets, representing millions of abundance observations, are likely unreliable or incorrect. Our new approach suggests that previous models are too simplistic, incorrectly estimating global abundance trends and often dramatically underestimating uncertainty, an aspect that is critical when translating global assessments into policy outcomes. Further, our approach also results in substantial improvements in abundance forecasting accuracy. Whilst our results do not improve the outlook for biodiversity, our framework does allow us to make more robust estimates of global wildlife abundance trends, which is critical for developing policy to protect our biosphere.

ecology↗

bioRxiv2020

METTL5, an 18S rRNA-specific m6A methyltransferase, modulates expression of stress response genes

RNA N6-methyladenosine (m6A) modification is present in different RNA molecules, including protein-coding mRNAs and non-coding RNAs such as ribosomal RNAs (rRNAs). Previous studies identified m6A in both the 18S and 28S rRNAs, but the roles of these methylation events are poorly understood due to the lack of knowledge of the responsible methyltransferases. Here, we report that mammalian METTL5, a member of a highly conserved methyltransferase family, specifically methylates adenosine 1832 (A1832) in the 18S rRNA in vivo and in vitro. We identify TRMT112 as a near stoichiometric partner of METTL5 important for the enzymatic activity of METTL5. By mapping the positions of translating ribosomes (Ribo-seq), we found translation of multiple stress response-related mRNAs, including Atf4 mRNA, is selectively reduced in the Mettl5 knockout (KO) mouse B16 melanoma cells. Atf4 is a key transcription factor that mediates the Integrated Stress Response (ISR), as exemplified by the Endoplasmic Reticulum (ER) stress. Consistently, transcription of ISR effector genes is reduced in Mettl5 KO cells during ER stress, suggesting a compromised ISR. Our findings reveal a new mechanism that regulates expression of stress response genes and suggest that chemical modifications of ribosomal RNAs may play a key role in selectively impacting translation and possibly ISR.

biochemistry↗

bioRxiv2020

Parallel cortical-brainstem pathways to attentional analgesia

Pain perception is diminished when attention is diverted. Our previous human fMRI study, using a 2x2 factorial design with thermal stimuli and concurrent visual attention task, linked the brainstem triad of locus coeruleus (LC), rostroventromedial medulla (RVM) and periaqueductal grey (PAG) to attentional analgesia. This study was repeated with a larger cohort, replicating our earlier findings. Pain intensity was encoded by the RVM, whilst activity in the contralateral LC correlated with the magnitude of attentional analgesia. Psycho-Physiological Interaction analysis informed subsequent Dynamic Causal Modelling and identified two parallel paths between forebrain and the brainstem regions involved in analgesia. These cortico-brainstem connections were modulated by attentional demand: a bidirectional anterior cingulate cortex (ACC) - right-LC loop, and a top-down influence of task on ACC-PAG-RVM. Under conditions of competing attentional demands the ACC recruits discrete brainstem circuits to modulate nociceptive input.

neuroscience↗

bioRxiv2018

Differential Profiles of Soluble and Cellular Toll-like Receptors (TLRs) 2 and 4 in Chronic Periodontitis.

Chronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells (SEC) in the saliva of patients with chronic periodontitis. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. The objective of this study was to investigate the potential value of salivary sTLR-2/4 and the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals in either periodontitis or gingivitis cohorts. The levels of sTLR-2/4 were measured by enzyme-linked immunosorbent assay (ELISA). SEC TLR-2/4 transcripts were quantitated by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while sTLR-2 and the paired SEC associated TLR-2 mRNA exhibited a direct correlation (r2=0.62), that of sTLR4 and SEC TLR-4 mRNA exhibited an inverse correlation (r2=0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in SECs could provide clinically relevant markers of disease progression from gingivitis to periodontitis.

immunology↗