Biology subjects

Law, R.

Publications and source records attributed to Law, R..

11 recordsLinked to original sources

bioRxiv2025

On the imbalance between production and exploitation of marine fish assemblages: a case study from the Celtic Seas

Sustainable management of marine ecosystems has to take into account the conservation of many species that are not themselves targets of fishing, in addition to those that are commercially exploited. Dynamic size-spectrum models suggest that fishing which leads species to have similar ratios of yield to production (i.e. similar exploitation ratios) is not sufficient to protect those that are rare: these species need to experience lower exploitation ratios. Here, the status of the demersal fish assemblage in the Celtic Seas is examined from the perspective of yield and production, using survey data collected over the period 2012 to 2016, and incorporating both common and rare species. The results give no evidence that rarer species have lower exploitation ratios than common ones. This suggests that current management methods are not not operating in a way that conserves the fish assemblage as a whole.

ecology↗

bioRxiv2023

Identification of Lactuca sativa transcription factors impacting resistance to Botrytis cinerea through predictive network inference

Lettuce is susceptible to a wide range of plant pathogens including the fungal pathogens Botrytis cinerea and Sclerotinia sclerotiorum, causal agents of grey mould and lettuce drop, respectively. Chemical control is routinely used but there is an urgent need to develop varieties with enhanced resistance given the economic and environmental costs of preventative pesticide sprays, the prevalence of fungicide-resistant isolates of both pathogens in the field, and the increasing withdrawal of approved fungicides through legislation. Resistance against Botrytis cinerea and Sclerotinia sclerotiorum is quantitative, governed by multiple small-medium impact loci, with plant responses involving large-scale transcriptional reprogramming. The elucidation of the gene regulatory networks (GRNs) mediating these responses will not only identify key transcriptional regulators but also interactions between regulators and show how the defence response is fine-tuned to a particular pathogen. We generated high-resolution (14 time points) time series expression data from lettuce leaves following mock-inoculation or inoculation with B. cinerea, capturing the dynamics of the transcriptional response to infection. Integrating this data with a time series dataset from S. sclerotiorum infection of lettuce identified a core set of 4362 genes similarly differentially expressed in response to both pathogens. Using the expression data for these core genes (with additional single time point data from 21 different lettuce accessions) we inferred a GRN underlying the lettuce defence response to these pathogens. Using the GRN, we have predicted and validated key regulators of lettuce immunity, identifying both positive (LsBOS1) and negative (LsNAC53) regulators of defence against B. cinerea, as well as downstream target genes. These data provide a high level of detail on defence-induced transcriptional change in a crop species and a GRN with the ability to predict transcription factors mediating disease resistance both in lettuce and other species.

plant biology↗

bioRxiv2023

Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4+ T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV- participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were rescued after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV- participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral blips in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4+ T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.

immunology↗

bioRxiv2022

Longitudinal Assessment of SARS-CoV-2 Specific T Cell Cytokine-Producing Responses for 1 Year Reveals Persistence of Multi-Cytokine Proliferative Responses, with Greater Immunity Associated with Disease Severity

Cellular-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 SARS-CoV-2-infected survivors over a one year post symptom onset (PSO) interval by ex vivo cytokine ELISpot assay. All subjects demonstrated SARS-CoV-2-specific IFN-{gamma}, IL-2, and Granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4+ T cells, targeted all structural proteins (Nucleocapsid, Membrane, Spike) except Envelope, with GzmB > IL-2 > IFN-{gamma}. Mathematical modeling predicted that: 1) cytokine responses peaked at 6 days for IFN-{gamma}, 36 days for IL-2, and 7 days for GzmB, 2) severe illness was associated with reduced IFN-{gamma} and GzmB, but increased IL-2 production rates, 3) males displayed greater production of IFN-{gamma}, whereas females produced more GzmB. Ex vivo responses declined over time with persistence of IL-2 in 86% and of IFN-{gamma} and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modelled to be 139 days ([~]4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the Nucleocapsid and Membrane regions. Both SARS-CoV-2-specific CD4+ and CD8+ T cell clones were able to kill target cells, though CD8 tended to be more potent. ImportanceOur findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control, shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and indicate robust persistence of T cell memory at least one year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.

immunology↗

bioRxiv2022

Maternal transmission as a symbiont sieve, and the absence of lactation in male mammals

Gut microbiomes of humans carry a complex symbiotic assemblage of microorganisms. As in all mammals, the special mode of feeding newborn infants through milk from the mammary gland enhances the opportunity for vertical transmission of the milk microbiome from parents to the gut microbiome of offspring. This has potential benefits, but it also brings with it some hazards for the host. Here we use mathematical and numerical models to demonstrate that vertical transmission from both parents would allow host populations to be invaded by microbiome elements that are deleterious. In contrast, vertical transmission, when restricted to one parent, acts as a sieve preventing the spread of such elements. We show that deleterious symbionts generate selection for uniparental transmission in host populations, and that this selective advantage is maintained in the presence of moderate horizontal transmission. Some vertical transmission from mother to infant is bound to happen in placental mammals. This paper therefore puts forward the hypothesis that the asymmetry between females and males, together with the hazards that come with biparental transmission of the milk microbiome, generate selection against male lactation in humans, and in mammals in general.

evolutionary biology↗

bioRxiv2021

Fishing for biodiversity

Fisheries are damaging, and seemingly incompatible with the conservation of marine ecosystems. Yet fish are an important source of food, and support the lives of many people in coastal communities. This paper considers an idea that a moderate intensity of fishing, appropriately scaled across species, could help in maintaining biodiversity, rather than reducing it. The scaling comes from an intuition that rates of fishing mortality of species should be kept in line with production rates of the species, a notion known as balanced harvesting. This places species conservation and exploitation on an equal footing in a single equation, showing quantitatively the relative levels of fishing mortality that species of different abundance can support. Using a dynamic model of a marine ecosystem, we give numerical evidence showing for the first time that fishing, if scaled in this way, can protect rarer species, while allowing some exploitation of species with greater production. This works because fishing mortality rates, when scaled by production, are density-dependent. Such fishing, operating adaptively to follow species production rates over time, contains a feedback that would help to protect species from overfishing in the presence of uncertainty about how marine ecosystems work.

ecology↗

bioRxiv2021

Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B

Safe and effective vaccines are needed to end the COVID-19 pandemic caused by SARS-CoV-2. Here we report the preclinical development of a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern (VOCs), including the B.1.1.7, B.1.351 and P.1 lineages. No adverse effects were induced by PTX-COVID19-B in both mice and hamsters. These preclinical results indicate that PTX-COVID19-B is safe and effective. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 1 clinical trial ongoing (ClinicalTrials.gov number: NCT04765436). One Sentence SummaryPTX-COVID19-B is a SARS-CoV-2 mRNA vaccine that is highly immunogenic, safe, and effective in preventing SARS-CoV-2 infection in mice and hamsters and is currently being evaluated in human clinical trials.

immunology↗

bioRxiv2021

Thalamocortical mechanisms regulating the relationship between transient beta events and human tactile perception

Transient neocortical events with high spectral power in the 15-29Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100-300ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, non-lemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300ms time scale to suppress sensory information. Further analysis showed that the same beta generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event faciliatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.

neuroscience↗

bioRxiv2020

Neural correlates of modal displacement and discourse-updating under (un)certainty

A hallmark of human thought is the ability to think about not just the actual world, but also about alternative ways the world could be. One way to study this contrast is through language. Language has grammatical devices for expressing possibilities and necessities, such as the words might or must. With these devices, called "modal expressions," we can study the actual vs. possible contrast in a highly controlled way. While factual utterances such as "There is a monster under my bed" update the here-and-now of a discourse model, a modal version of this sentence, "There might be a monster under my bed," displaces from the here-and-now and merely postulates a possibility. We used magnetoencephalography (MEG) to test whether the processes of discourse updating and modal displacement dissociate in the brain. Factual and modal utterances were embedded in short narratives, and across two experiments, factual expressions increased the measured activity over modal expressions. However, the localization of the increase appeared to depend on perspective: signal localizing in right temporo-parietal areas increased when updating others beliefs, while frontal medial areas seem sensitive to updating ones own beliefs. The presence of modal displacement did not elevate MEG signal strength in any of our analyses. In sum, this study identifies potential neural signatures of the process by which facts get added to our mental representation of the world.

neuroscience↗

bioRxiv2020

Lists with and without syntax: A new approach to measuring the neural processing of syntax

In the neurobiology of language, a fundamental challenge is deconfounding syntax from semantics. Changes in syntactic structure usually correlate with changes in meaning. We approached this challenge from a new angle. We deployed word lists, which are usually the unstructured control in studies of syntax, as both the test and the control stimulus. Three-noun lists (lamps, dolls, guitars) were embedded in sentences (The eccentric man hoarded lamps, dolls, guitars...) and in longer lists (forks, pen, toilet, rodeo, graves, drums, mulch, lamps, dolls, guitars...). This allowed us to perfectly control both lexical characteristics and local combinatorics: the same words occurred in both conditions and in neither case did the list items locally compose into phrases (e.g. lamps and dolls do not form a phrase). But in one case, the list partakes in a syntactic tree, while in the other, it does not. Being embedded inside a syntactic tree increased source-localized MEG activity at ~250-300ms from word onset in the left inferior frontal cortex, at ~300-350ms in the left anterior temporal lobe and, most reliably, at ~330-400ms in left posterior temporal cortex. In contrast, effects of semantic association strength, which we also varied, localized in left temporo-parietal cortex, with high associations increasing activity at around 400ms. This dissociation offers a novel characterization of the structure vs. meaning contrast in the brain: The fronto-temporal network that is familiar from studies of sentence processing can be driven by the sheer presence of global sentence structure, while associative semantics has a more posterior neural signature. SIGNIFICANCE STATEMENTHuman languages all have a syntax, which both enables the infinitude of linguistic creativity and determines what is grammatical in a language. The neurobiology of syntactic processing has, however, been challenging to characterize despite decades of study. One reason is pure manipulations of syntax are difficult to design. The approach here offers a perfect control of two variables that are notoriously hard to keep constant when syntax is manipulated: word meaning and phrasal combinatorics. The same noun lists occurred inside longer lists and sentences, while semantic associations also varied. Our MEG results show that classic fronto-temporal language regions can be driven by sentence structure even when local semantic contributions are absent. In contrast, the left temporo-parietal junction tracks associative relationships.

neuroscience↗

bioRxiv2017

The rate of transient beta frequency events predicts impaired function across tasks and species

Beta frequency oscillations (15-29Hz) are among the most prominent signatures of brain activity. Beta power is predictive of many healthy and abnormal behaviors, including perception, attention and motor action. Recent evidence shows that in non-averaged signals, beta can emerge as transient high-power \"events\". As such, functionally relevant differences in averaged power across time and trials can reflect accumulated changes in the number, power, duration, and/or frequency span of the events. We show for the first time that functionally relevant differences in averaged prestimulus beta power in human sensory neocortex reflects a difference in the number of high-power beta events per trial, i.e., the rate of events. Further, high power beta events close to the time of the stimulus were more likely to impair perception. This result is consistent across detection and attention tasks in human magnetoencephalography (MEG) and is conserved in local field potential (LFP) recordings of mice performing a detection task. Our findings suggest transient brain rhythms are best viewed as a \"rate metric\" in their impact on function, and provides a new framework for understanding and manipulating functionally relevant rhythmic events.

neuroscience↗