Biology subjects

Harrison, M.

Publications and source records attributed to Harrison, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Transgene Expression Kinetics and Replication Potential of Recombinant Adenovirus Serotype 4 in a Mouse Model and its Use as a Herpes Simplex Virus Vaccine

Human adenovirus serotype 4 (Ad4) is used as a replication-competent oral vaccine that safely and effectively prevents Ad4 respiratory illness in US military personnel. Recombinant Ad4 vaccine candidates elicit mucosal and systemic immune responses against respiratory viruses in hamsters, nonhuman primates, and humans. Although evaluation of Ad4 vaccine candidates in mice would be extremely useful given the large number of immunologic tools available, this has been limited by concerns about a lack of viral replication in these animals. Here we generated recombinant Ad4 vectors that express either luciferase (Ad4-Luc) or herpes simplex virus type 2 (HSV-2) glycoprotein D (Ad4-gD2) to identify transgene expression kinetics, the presence of Ad4 vector replication, and HSV-2 immune responses and protection against HSV-2 infection. Local luciferase activity was observed from 7 hours to 20 days after intranasal inoculation of BALB/c and humanized mice. Subsequent inoculations with Ad4-Luc showed reduced luciferase expression in BALB/c mice, but robust expression in humanized mice, suggesting an immune response to the vector in wild-type mice. Ad4 DNA, but not luciferase activity, was reduced in the lungs of BALB/c mice treated with cidofovir before inoculation with Ad4, implying that Ad4 replicated, albeit at a low level, in the lungs. Intranasal vaccination of mice with Ad4-gD2 resulted in HSV-2 neutralizing antibody in the serum, and after HSV-2 intravaginal challenge reduced disease scores, increased survival, and reduced shedding. Overall, the BALB/c mouse model is semi-permissive to Ad4 mucosal infection, but transgene expression is sufficient for the study of Ad4-based vaccine candidates. ImportanceMucosal surfaces serve as the primary site of infection and shedding for many viral pathogens. Immune responses at mucosal sites provide protection, but few mucosal vaccines are licensed. The oral replication-competent adenovirus serotype 4 (Ad4) vaccine is used to prevent respiratory illness in military recruits, has an extraordinary record of safety and efficacy and has been tested as a recombinant platform for other viruses. Further development of this vaccine platform has been partially hindered by the perceived inability to evaluate vaccine candidates in mice. Here we characterize recombinant Ad4 transgene expression kinetics and viral replication after inoculation at various sites and show protection against herpes simplex virus type 2 (HSV-2) genital disease in mice after intranasal vaccination. We show that Ad4 can induce protective efficacy, even in a semi-permissive mouse model, suggesting this is a promising vector for HSV-2 and potentially other viral pathogens.

immunology↗

bioRxiv2026

DOME Copilot: Making transparency and reproducibility for artificial intelligence methods simple

Artificial intelligence (AI) methods are transforming life science research and witnessing unprecedented adoption across literature. While AI is driving impactful discoveries, this rapid growth in application has inundated researchers with poorly described models and datasets which lack transparency, impeding reusability and eroding trust. The DOME Recommendations aimed to address this issue and established structured reporting guidelines to standardize AI methodology descriptions. However, the need to manually create these comprehensive disclosures imposed a major bottleneck, requiring substantial effort from authors to comply. To bridge this gap, we present DOME Copilot, an open-source, easily deployable system that automates the generation of transparent AI methodology reports supplementing publications. Evaluated against a benchmark of human-created annotations, DOME Copilot was determined to match or exceed manual annotation quality across the majority of reporting fields while reducing the creation time from hours to minutes. Ultimately, the system provides a novel and scalable solution to restore confidence in complex life science AI method publications.

bioinformatics↗

bioRxiv2026

Development and evaluation of a cost-effective, mid-density SNP array as a sorghum community genotyping resource

The development of accessible and cost-effective genotyping platforms is essential to accelerate genetic gain in crop improvement. To address the U.S. sorghum communitys need for a standardized, mid-density genotyping resource, we developed and validated a targeted single-nucleotide polymorphism (SNP) array using the PlexSeq next-generation sequencing (NGS) platform. The resulting genotyping array includes 2,421 SNPs spanning all ten Sorghum bicolor chromosomes and integrates trait-linked and quality control markers selected by public and private stakeholders. Genotyping 2,726 diverse accessions, including the Sorghum Association Panel (SAP), demonstrated high call rates (>90% for most samples and markers), low missing data, and accurate resolution of population structure consistent with prior whole-genome studies. In comparative genomic prediction analyses, the mid-density array performed equivalently to high-density genotype-by-sequencing (GBS) platforms for key traits such as grain yield and plant height across multi-environment trials. Designed for broad utility in breeding pipelines, the array enables marker-assisted selection, genomic prediction, identity verification, and germplasm quality control. Moreover, its adoption by the USDA National Plant Germplasm System facilitates the curation of genebanks and the management of core collections. This community-driven genotyping platform offers a scalable, reproducible, and customizable tool to support molecular breeding in sorghum and underscores the value of targeted marker systems in resource-optimized crop improvement programs.

plant biology↗

bioRxiv2026

Simplifying principles that underlie the highly complex peptide motif of the promiscuous chicken class I molecule, BF2*21:01

In chickens and humans, classical class I molecules of the major histocompatibility complex (MHC) have a spectrum of correlated properties, including cell surface expression and peptide repertoire. Understanding the impact of these promiscuous generalists and fastidious specialists is of considerable interest. The promiscuous BF2 molecule from the chicken B21 haplotype, BF2*21:01, binds a wide range of peptides by remodelling the peptide-binding site, allowing co-variation of the anchor residues at peptide positions P2 and Pc-2, and binding of an anchor residue at Pc. Using in vitro refolding assays with peptides and peptide libraries, determining thermostability and crystal structures, and analysing a chicken B21 cell line by immunopeptidomics, we found that BF2*21:01 will accommodate many possible combinations at P2 and Pc-2, as well as several hydrophobic amino acids at Pc. However, marked preferences for particular peptide lengths, particular amino acids at the three anchor residues, and particular combinations of amino acids at P2 and Pc-2 as well as at P3 and Pc-3 together lead to high frequencies of major peptides while still allowing the possibility of presenting a wide peptide repertoire. These simplifying principles may eventually allow predictions of pathogen peptides with stable binding for this iconic promiscuous class I molecule, as well as providing the data for more sophisticated peptide prediction methods.

immunology↗

bioRxiv2026

Pioneer-factor activity requires stable chromatin occupancy mediated by both sequence-specific binding and disordered protein domains

Pioneer transcription factors overcome the restrictive barrier imposed by chromatin to drive cell-fate specification, yet how their domains collectively support this activity remains unclear. Here, we use the deeply conserved pioneer factor Grainy head to define the protein-intrinsic features that govern pioneering activity. By integrating biochemistry, genomics and quantitative live-cell imaging, we determined that both the conserved DNA-binding domain and the extended, intrinsically disordered N-terminus are required for the stable chromatin occupancy that supports access to closed chromatin and the induction of chromatin accessibility. The disordered N-terminus supports pioneer activity through interactions that do not rely on strict amino acid sequence but instead overall composition. While our results show that pioneering activity depends on the combinatorial contributions of structured and disordered domains, mitotic retention depends solely on sequence-specific DNA binding. These results support stable chromatin occupancy mediated by multiple protein domains as necessary for pioneering function and that this is separable from the mechanisms required for mitotic retention.

molecular biology↗

bioRxiv2026

Intranasal Replicating Adenovirus type 4-SARS-CoV-2 Recombinants Induce Superior Immune Response Durability and Efficacy in Preclinical Testing Compared to Standard Intramuscular Vaccines

The portfolio of next generation COVID-19 vaccines would benefit from candidates that induce durable systemic and mucosal immune responses that would lessen person-to-person transmission. We constructed an intranasal (IN) replication-competent adenovirus type 4 recombinant platform to express SARS-CoV-2 Spike variants (Ad4-S) and assessed immunogenicity and efficacy in the Syrian hamster model. Although both IN Ad4-S and intramuscular (IM) vaccines (Ad26.CoV2.S and mRNA-1273) induced serum binding antibodies, only Ad4-S induced a robust mucosal response in the nasal cavity. IN Ad4-S vaccination induced serum neutralizing titers equivalent to or greater than IM vaccination but more durable up to 6 months. Upon challenge, IN immunization also resulted in less weight loss, greater breadth and durability of restriction of viral replication, and less lung pathology than IM immunization up to 268 days after immunization. These data support the potential of the IN Ad4 vaccine platform to reduce transmission of SARS-CoV-2 and other respiratory viruses with pandemic potential.

immunology↗

bioRxiv2025

HIV-associated non-Hodgkin lymphoma tumor-microenvironment axes differ by EBV status across cellular origins

Non-Hodgkin Lymphoma (NHL) is the main cancer-related mortality for people living with HIV (PLWH). NHL genetic and molecular classifications have been intensely studied and correlated with clinical outcomes, but critical unanswered questions relevant to malignancy persist. For example, tumors positive for Epstein-Barr virus (EBV) are aggressive and account for 30-50% of HIV-associated NHLs, yet insights on the nature of EBV in NHL pathogenesis or potential therapeutic vulnerabilities have been limited. Here, we examined HIV-associated NHLs stratified by histopathologic classification, cell of origin (COO), molecular subtype, and EBV status using genome-wide spatial transcriptomic analyses. Tumor tissues in EBV+ HIV-NHLs displayed enriched expression of mitochondrial respiration and purine metabolism signatures versus EBV- tumors. Immune infiltration of EBV+ tumors was limited, and immune and stromal regions of EBV+ HIV-NHLs displayed upregulation of the gene for the iron exporter ferroportin (SLC40A1), indicating immunosuppressive macrophage polarization. An immunosuppressive SPP1-CD44 axis and oncogenic GAS6-AXL interaction between tumor and stroma were specifically predicted for EBV+ HIV-NHLs with plasmablastic features. Tumor microenvironment (TME) similarities to secondary lymphoid tissues such as inverse CXCL12-CXCL13 gradients and evidence of matching between tumor B cell phenotypes and reticular cell signatures were also observed. Finally, we developed a simple yet flexible approach to quantify expression gradients and cell proximity to annotated regions. Thus, this study highlights potential avenues for NHL therapy tailored by EBV status and provides a unique resource to examine tumor-TME interactions in the HIV-immunocompromised context. Key PointsO_LISpatial transcriptomic landscapes resolve cell-of-origin- and EBV-associated HIV-NHL heterogeneity including immunosuppressive myeloid responses to EBV+ tumors C_LIO_LISpatial gradients including CXCL12 and CXCL13 indicate that tumor-stromal interactions mimic lymphoid tissue organization and depend on B cell development stage C_LIO_LIDevelopment of a direction-agnostic method to calculate spatial expression gradients relative to annotated tissue and cell types of interest C_LIO_LIPredicted pharmacologic vulnerabilities in clinical samples are replicated in vitro and confirmed by small molecule screening C_LI

cancer biology↗

bioRxiv2025

Hydration free energy is a significant predictor of globular protein incorporation into condensates

Membraneless organelles (MLOs) are assemblies of biomolecules, which function without a dividing lipid membrane in a cellular environment. These MLOs, termed biomolecular condensates, are commonly formed by the thermodynamic process of liquid-liquid phase separation (LLPS) and assembly of large numbers of proteins, nucleic acids and co-solvent molecules. Within MLOs, certain biomolecule types are particularly causative of phase separation, and are termed "scaffolds" as they provide the major driving forces for self-assembly. Other molecules that are present in a condensate, but are less causative than the scaffold molecules are termed "clients". Much effort has recently decoded many of the molecular interactions underlying LLPS in search of predicting equilibrium concentrations and materials properties of condensates. In this work, we provide a simple computational approach to predict the partitioning of globular protein clients into condensates primarily composed of disordered protein scaffolds. Specifically, we use multiple methods to calculate hydration free energy of a series of globular proteins, and find that hydration free energy is relatively well-correlated with the partition coefficient of these proteins into condensates. We then provide a comparison of different hydration free energy predictors and discuss why some may provide a more accurate prediction of partitioning. Finally, we discuss the shortcomings of hydration free energy as a predictor by identifying other possible confounding factors such as specific interactions, charge matching, and differential solvation inside a condensate, which will aid in making more robust predictions in future studies trained on more diverse data sets. Significance StatementUnderstanding the extent to which molecules can partition into biomolecular condensates is crucial for deciphering cellular organization and function. This study introduces a simple computational approach to predict the partitioning of globular proteins into condensates using hydration free energy as a key predictor, which can be calculated from static globular protein structures. By comparing different hydration free energy predictors, we also higlight the limitations of relying solely on this hydration free energy, emphasizing the need to consider other molecular factors. We finally analyze the shortcomings of the hydration free energy precitions, and discuss other factors that contribute to partitioning of clients into condensates, namely specific interactions and net charge of the scaffold molecules, and different properties of water in the condensate.

biophysics↗

bioRxiv2025

Horizontal gene transfers are widespread across termite genomes but do not confer metabolic innovations

Horizontal gene transfer (HGT), the transmission of genetic material across species, is an important innovation source in prokaryotes. In contrast, its significance is unclear in many eukaryotes, including insects. Here, we used high-quality genomes of 45 termites and two cockroaches to investigate HGTs across blattodean genomes. We identified 289 genes and 2,494 pseudogenes classified into 168 orthologous groups originating from an estimated 281 HGT events. Wolbachia represented the primary HGT source, while termite gut bacteria and the cockroach endosymbiont Blattabacterium did not contribute meaningfully to HGTs. Most horizontally acquired genes descended from recent and species-specific HGTs, experienced frequent duplications and pseudogenizations, and accumulated substitutions faster than synonymous sites of native protein-coding genes. Genes frequently transferred horizontally to termite genomes included mobile genetic elements and genetic information processing genes. Our results indicate that termites continuously acquired genes through HGT, which they soon lost, leaving few horizontally acquired genes conserved across lineages.

genomics↗

bioRxiv2025

Unravelling termite evolution with 47 high-resolution genome assemblies

Termites are a lineage of social cockroaches abundant in tropical ecosystems where they are key decomposers of organic matter from wood to soil. Despite their ecological significance, only a handful of reference-quality termite genomes have been sequenced, which is insufficient to unravel the genetic mechanisms that have contributed to their ecological success. Here, we performed sequencing and hybrid assembly of 45 taxonomically and ecologically diverse termites and two cockroaches, resulting in haplotype-merged genome assemblies of 47 species, 22 of which were near-chromosome level. Next, we examined the link between termite dietary evolution and major genomic events. We found that Termitidae, which include [~]80% of described termite species, have larger genomes with more genes and a higher proportion of transposons than other termites. Our analyses identified a gene number expansion early in the evolution of Termitidae, including an expansion of the repertoire of CAZymes, the genes involved in lignocellulose degradation. Notably, this expansion of genomes and gene repertoires coincided with the origin of soil-feeding in Termitidae and remained unchanged in lineages that secondarily reverted to a wood-based diet. Overall, our sequencing effort multiplied the number of available termite genomes by six and provided unprecedented insights into the genome evolution of the most ancient lineage of social insects.

genomics↗

bioRxiv2024

Reduced regulatory complexity associated with the evolutionary transition to sociality from cockroaches to termites despite evolutionary parallels with Hymenoptera

The degree of phenotypic diversity within social species has previously been associated with more complex genetic regulation both in cis and trans contexts. Transcription factors (TFs) being key to genetic regulation, have been studied in the origins of eusociality in Hymenoptera (bees, ants and wasps) but less so in Blattodea (cockroaches and termites). Here we show that the social transition in Blattodea, from cockroaches to termites, displays similar patterns of regulatory change to those found in Hymenoptera. Specifically, by analysing 3 cockroach and 5 termite genomes, we find more TF families with relaxed selection compared to intensified selection and lineage-specific gene family expansions in termites, which has also been reported in Hymenoptera. We also find that genes under selection support neotenic caste determination. We find there are key differences in Blattodea TF regulation in comparison with Hymenoptera with contractions in TF gene families and no compensatory change in TF DNA binding motifs either in frequency or diversity in TF promoter regions. Furthermore, we show that an increase in social complexity leads to greater diversity in TF activating domains, one of the evolutionary and structural building blocks of TFs, meanwhile, DNA-binding domains, undergo very little change. This study highlights similarities in social transitions between Hymenoptera and Blattodea, with evidence of large changes in transcriptional regulation followed by lineage specific adaptations. Our results indicate that the transcriptional diversity linked to social complexity is not attributable to transcription factors, but is instead likely driven by an alternative mechanism.. Significance statementIt has been widely reported that increased phenotypic complexity, particularly arising from social transitions, is often accompanied by increased regulatory complexity followed by lineage-specific adaptations. While extensively studied in Hymenoptera (bees, ants, and wasps), it has been less explored in Blattodea (cockroaches and termites). By examining the evolution of transcription factors across Blattodea, we investigated the regulatory changes associated with this social transition. Our study reveals that increased social complexity in Blattodea is accompanied by a reduction in regulatory complexity, including decreases in transcription factor numbers and no compensatory change in TF promoter binding site diversity or regulation. This study highlights that social transitions in Blattodea and Hymenoptera share a common pattern of large regulatory changes followed by lineage-specific adaptations.

evolutionary biology↗

bioRxiv2024

Comparative study on the virulence of mycobacteriophages

The global tuberculosis (TB) epidemic affected 10 million people and caused 1.3 million deaths in 2022 alone. Multidrug-resistant TB is successfully treated in less than 60% of cases by long, expensive and aggressive treatments. Mycobacteriophages, viruses that can infect bacteria such as Mycobacterium tuberculosis--the species responsible for TB, have the potential to redefine TB prevention and treatments. However, the development of phage-based products necessitates the assessment of numerous parameters, including virulence and adsorption, to ensure their performance and quality. In this work, we characterized the virulence of three different mycobacteriophages (Fionnbharth, Muddy and D29), alone and as cocktails, against a TB model host (Mycobacterium smegmatis) under planktonic and early-stage biofilm growth conditions. Phage D29 and cocktails containing D29 had the highest virulence under all conditions. Interestingly, phages Fionnbharth and Muddy and their combination showed higher virulence against early-stage biofilm than against the planktonic phenotype. Adsorption assays indicated that all three phages had lower adsorption efficiencies on the early-stage biofilm phenotype than on the planktonic one, suggesting a reduced availability of receptors in the former. Given that, despite these lower adsorption efficiencies, the virulence of the phages and phage cocktails was either unchanged or higher against the early-stage biofilm, this phenotype must display properties that are favorable to other steps of the infection process. These results inform us on the dynamics of mycobacteriophage infections, alone and in cocktail formulations, under different host growth conditions, and serve as a basis for the development of phage products targeting mycobacteria biofilms.

microbiology↗

bioRxiv2024

Enabling preprint discovery, evaluation, and analysis with Europe PMC

Preprints provide an indispensable tool for rapid and open communication of early research findings. Preprints can also be revised and improved based on scientific commentary uncoupled from journal-organised peer review. The uptake of preprints in the life sciences has increased significantly in recent years, especially during the COVID-19 pandemic, when immediate access to research findings became crucial to address the global health emergency. With ongoing expansion of new preprint servers, improving discoverability of preprints is a necessary step to facilitate wider sharing of the science reported in preprints. To address the challenges of preprint visibility and reuse, Europe PMC, an open database of life science literature, began indexing preprint abstracts and metadata from several platforms in July 2018. Since then, Europe PMC has continued to increase coverage through addition of new servers, and expanded its preprint initiative to include the full text of preprints related to COVID-19 in July 2020 and then the full text of preprints supported by the Europe PMC funder consortium in April 2022. The preprint collection can be searched via the website and programmatically, with abstracts and the open access full text of COVID-19 and Europe PMC funder preprint subsets available for bulk download in a standard machine-readable JATS XML format. This enables automated information extraction for large-scale analyses of the preprint corpus, accelerating scientific research of the preprint literature itself. This publication describes steps taken to build trust, improve discoverability, and support reuse of life science preprints in Europe PMC. Here we discuss the benefits of indexing preprints alongside peer-reviewed publications, and challenges associated with this process.

scientific communication and education↗

bioRxiv2024

Lit-OTAR Framework for Extracting Biological Evidences from Literature

The lit-OTAR framework, developed through a collaboration between Europe PMC and Open Targets, leverages deep learning to revolutionise drug discovery by extracting evidence from scientific literature for drug target identification and validation. This novel framework combines Named Entity Recognition (NER) for identifying gene/protein (target), disease, organism, and chemical/drug within scientific texts, and entity normalisation to map these entities to databases like Ensembl, Experimental Factor Ontology (EFO), and ChEMBL. Continuously operational, it has processed over 39 million abstracts and 4.5 million full-text articles and preprints to date, identifying more than 48.5 million unique associations that significantly help accelerate the drug discovery process and scientific research (> 29.9m distinct target-disease, 11.8m distinct target-drug and 8.3m distinct disease-drug relationships). The results are made accessible through the Open Targets Platform (https://platform.opentargets.org/) as well as Europe PMC website (SciLite web app) and annotations API (https://europepmc.org/annotationsapi).

bioinformatics↗

bioRxiv2024

Cellular mechanotransduction of human osteoblasts in microgravity

Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, 4 microfluidic chips capable of measuring single-cell mechanics of hFOBs via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. Our analysis revealed slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell behavior and signaling in space.

cell biology↗

bioRxiv2023

Protein-intrinsic properties and epigenetic effects regulate pioneer-factor binding and function

Chromatin is a barrier to the binding of many transcription factors. By contrast, pioneer factors access nucleosomal targets and promote chromatin opening. Despite binding to target motifs in closed chromatin, many pioneer factors display cell-type specific binding and activity. The mechanisms governing pioneer-factor occupancy and the relationship between chromatin occupancy and opening remain unclear. We studied three Drosophila transcription factors with distinct DNA-binding domains and biological functions: Zelda, Grainy head, and Twist. We demonstrated that the level of chromatin occupancy is a key determinant of pioneering activity. Multiple factors regulate occupancy, including motif content, local chromatin, and protein concentration. Regions outside the DNA-binding domain are required for binding and chromatin opening. Our results show that pioneering activity is not a binary feature intrinsic to a protein but occurs on a spectrum and is regulated by a variety of protein-intrinsic and cell-type-specific features.

developmental biology↗

bioRxiv2022

The Ecosystem Integrity Index: a novel measure of terrestrial ecosystem integrity with global coverage

While the importance of ecosystem integrity has long been recognised (Leopold, 1949), conservation science has tended to focus on measuring and monitoring species and habitats, avoiding the complexities of working at the ecosystem level. Ecosystems are highly dynamic, defined by both living and non-living components as well as their interactions (CBD, 1992), making it difficult to assess baseline levels of integrity. We present a novel index that represents the integrity of all terrestrial ecosystems globally at 1km2 resolution: the Ecosystem Integrity Index (EII). The index provides a simple, yet scientifically robust, way of measuring, monitoring and reporting on ecosystem integrity. It is formed of three components; structural, compositional and functional integrity, and measured against a natural (current potential) baseline on a scale of 0 to 1. We find that ecosystem integrity is severely impacted in terrestrial areas across the globe with approximately one fifth of all ecosystems and one quarter of all ecoregions having lost, on average, over half of their ecosystem integrity. At a national scale, we estimate similar challenges with 115 nations or territories having lost, on average, over half of their ecosystem integrity. This presents a significant threat for humanity as such levels of degradation are likely to be linked to substantial declines in the ecosystem services on which humanity is reliant. The EII has been developed principally to help national governments measure and report on Goal A of the Kunming-Montreal Global Biodiversity Framework (GBF) (CBD, 2022a), for which it has been listed as a Component Indicator. The EII will also be useful in helping non-state actors measure and report their contributions to the GBF and is listed as an indicator by both the Taskforce for Nature-Related Financial Disclosures (TNFD) (TNFD, 2023) and the Science Based Targets Network (SBTN) (SBTN, 2023). The EII aims to enable these actors to make informed decisions on the conservation, restoration and sustainable use of ecosystems for which they are wholly or partly responsible. We propose that with sufficient effort, ecosystem integrity can be restored and contribute towards the GBFs vision of living in harmony with nature, resulting in the safeguarding of the ecosystem services on which humanity depends.

ecology↗

bioRxiv2022

PELP: accounting for missing data in neural time series by Periodic Estimation of Lost Packets

ObjectiveImplanted electrical stimulators with sensing capabilities have enabled the development of closed-loop neuromodulation therapies capable of responding to patient needs in real-time. Through a combination of rechargeable technologies and wireless data transmission, it is now possible for researchers to acquire extensive neural recordings from human participants in naturalistic settings using these bidirectional devices. However, data losses during wireless transmission hamper processing and the identification of neural signals of interest, driving the need for methodologies to properly estimate the impact of data loss. ApproachTo accurately reconstruct the timing of data containing losses, we have developed a method called Periodic Estimation of Lost Packets (PELP) to precisely determine the number of samples lost from implanted recordings during active stimulation. PELP leverages a data-driven procedure for determining the period of stimulation and the knowledge that stimulation continues identically during periods where data are missing to accurately account for the number of samples lost. Main resultsUsing simulated stimulation added to collected human EEG data, we show that PELP is robust to a range of stimulation waveforms and noise characteristics. Lastly, we successfully applied PELP to local field potential (LFP) recordings from an implanted, bidirectional device using data recorded in the clinic and the patients own home. SignificanceBy effectively accounting for the timing of missing data, PELP enables the analysis of complex, naturalistic neural time series data from bidirectional implanted devices aiding in the development of novel therapeutic approaches. NCT04806516 (ClinicalTrials.gov).

neuroscience↗