Biology subjects

Pickering, A.

Publications and source records attributed to Pickering, A..

10 recordsLinked to original sources

bioRxiv2026

PAMalytics: a no-code application for structured validation of bioacoustic detections

1. Passive acoustic monitoring (PAM) is increasingly used for ecological research, biodiversity monitoring, assessment, and reporting. Automated species classifiers make it feasible to process large audio datasets but generate numerous detections that often need validation before use in downstream analyses or formal outputs. 2. Method development in PAM has focused on classifier building and downstream models that account for imperfect detection, yet the practical step between these - post-classification validation - remains weakly supported and is often implemented through ad hoc workflows. This increases manual handling, creates scope for transcription or consolidation errors, limits transparency and makes it difficult to document what was reviewed. 3. We introduce PAMalytics, an open-source, no-code, local browser-based application to support post-classification validation as a standardised workflow stage. PAMalytics ingests detections from any classifier, allows users to define how detections are sampled for review, and presents selected detections alongside their spectrograms with audio playback in one unified interface. Sampling strategy and review decisions are tracked alongside reviewer identity improving traceability and reproducibility across the validation workflow. 4. Case studies with Conservation International Cambodia and Imperial College London demonstrate PAMalytics in two validation settings. In Cambodia, gibbon predictions from a large, uneven dataset were sampled within sites, with likely classifier errors prioritised for validation. At Imperial, Amazon bird detections were sampled across each species classifier-confidence range before biodiversity metrics were derived. In both cases, PAMalytics reduced manual handling and validation time. By turning an ad hoc step into an accessible, structured workflow for conservation practitioners, PAMalytics fills a practical gap in the PAM bioacoustics pipeline and strengthens the link between automated detections and evidence used in biodiversity monitoring and reporting.

ecology↗

bioRxiv2026

Trait misalignment risk in North American forests under climate change

Climate change is expected to alter forest community composition and functioning, with consequences for the ecosystem services forests provide. However, most macroecological projections focus on individual species distributions and offer limited insight into whether entire communities will remain functionally compatible with future climatic conditions. Here we quantify the risk that present-day forest communities will become functionally misaligned with projected climates using a trait-based approach. We analysed forest inventory data from more than 42,000 mature plots across the United States and Canada. For each plot we estimated community-weighted means for 24 functional traits describing leaf economics, hydraulic function, wood structure, abiotic tolerances and symbiotic strategies. We modelled relationships between community functional composition and environmental conditions, and used these relationships to estimate the trait profiles most compatible with projected late-century climates (2080-2100). Trait-environment misalignment (TEM) risk was quantified as the multivariate distance between current community trait composition and the trait profile associated with the projected future climate at each location, accounting for covariance among traits and intraspecific trait variation. Projected climatic conditions favour trait combinations associated with greater hydraulic capacity and reduced cold and shade tolerance. However, the magnitude of functional misalignment varies strongly across space. The highest TEM risk occurs in high-latitude and montane conifer forests across western and central North America, whereas many mid-latitude broadleaf and mixed forests show lower risk because projected climatic changes reinforce existing drought-adapted functional strategies. Critically, high species richness was the strongest predictor of reduced risk, reinforcing the importance of biodiversity in buffering against adverse outcomes. Our results suggest that many forests are projected to experience climatic conditions associated with functional strategies that differ from those characterising the current community. By identifying where the largest functional adjustments are implied, this trait-based framework provides a scalable way to pinpoint forests most likely to experience suboptimal climate conditions and to prioritise monitoring and climate-adapted management.

ecology↗

bioRxiv2025

Sustainable cattle management by communities supports African wildlife

Community-based conservation (CBC) initiatives aim to reconcile biodiversity protection with local livelihoods, yet their effectiveness in protecting wildlife remains uncertain, often hinging on local management1,2. We evaluated a globally significant CBC model in Kenyas Greater Maasai Mara Ecosystem (GME), where conservancies, run jointly by Maasai landowners and the tourism sector, employ rotational cattle grazing to support both wildlife and pastoralism3,4. Using a [~]1200 km2 grid of 180 camera traps across gradients of livestock pressure in Maasai Mara National Reserve and three conservancies in 2018, we collected and analysed over 2 million images with a customised AI-powered pipeline. We found a positive impact of observed cattle pressure on mammal community occupancy and species richness, except for at the highest levels of cattle grazing. However, sheep and goat grazing and proximity to infrastructure had a negative impact. These results provide evidence that wildlife and pastoralism can coexist under community-led stewardship5, but only with active management and targeted control of emerging threats. AI tools such as our image classifier may contribute to more adaptive community-led management of these areas6. As conservation policy shifts beyond formal protected areas, our findings support CBC as a scalable model for conserving biodiversity within working landscapes, offering a pathway to meet global targets while maintaining local livelihoods7.

ecology↗

bioRxiv2025

A single transcriptional regulator is crucial for the adaptation of Staphylococcus aureus to diverse niches

The adaptation of versatile multi-host pathogens to various hosts and various niches within hosts is often still poorly understood. The alternative Sigma factor B (SigB) is the master regulator of the general stress response of most gram-positive bacteria, which is a classic case of adaptive plasticity. In Staphylococcus aureus, SigB appears co-opted to function as a switch between intracellular and extracellular niches. During bovine mastitis, low SigB-activity confers an advantage in the milk-rich extracellular niche of the bovine udder. We show that narrowly adapted SigB-deficient strains evolved repeatedly from phenotypically plastic SigB-wildtype strains during persistent mastitis. This genetic assimilation appears driven by the cost of phenotypic plasticity: long time lags in adapting to milk and slow growth. Surprisingly, we observe that mutations causing SigB-deficiency allow even human isolates to grow in milk. While host adaptation often proceeds by mobile genetic elements exchanged between strains, we show how a master regulator in the core genome can drive niche adaptation.

microbiology↗

bioRxiv2024

β-Amyloid impairs Proteasome structure and function. Proteasome activation mitigates amyloid induced toxicity and cognitive deficits

BackgroundImpaired proteasome activity is a robust and reproducible feature in Alzheimers disease (AD) patients and animal models. Although amyloid beta (A{beta}) may inhibit proteasomes, it is unclear if this reflects direct structural interference or indirect toxicity. The proteasome controls a myriad of critical neuronal processes with its disruption potentially driving downstream AD pathology. MethodsWe examined the direct impact of distinct A{beta} forms on proteasome structure, dynamics, and function by evaluating enzyme activity and morphology by atomic force microscopy (AFM) and native-gel electrophoresis. To prevent A{beta}-induced impairments in vitro and in AD animal models, we used allosteric proteasome activating peptidomimetics. We characterized their interactions with proteasome by AI enhanced in silico docking. ResultsToxic soluble A{beta}42 oligomers selectively inhibit 20S and 26S proteasome activity, while monomeric and fibrillar forms and A{beta}40 show minimal inhibitory effects. Morphometric analysis of AFM images suggests A{beta}42 oligomers bind laterally to the 20S proteasomes, and impair proteasome dynamics by disabling gate opening, critical for catalytic activity. Oligomer-decorated proteasomes are locked in catalytically inert cycling between closed and intermediate gate conformations. Oligomeric A{beta}42 also induces disassembly of the 26S complex, increasing content of free 20S cores. Importantly, we show proteasome dysfunction induced by oligomeric A{beta}42 is both preventable and reversible by employing an allosteric proteasome activator TAT-DEN, promoting gate opening and restoring enzymatic activity with the full-cycle of conformational transitions in oligomers-treated proteasomes. In cellular and animal models, restoring proteasome function via TAT-DEN mitigated A{beta}-induced cell death, spatial learning/memory deficits, and survival impairments, even under conditions of pre-established A{beta} deficits. ConclusionsOligomeric A{beta}42 decorates the lateral sides of the 20S proteasome restricting cycling between conformations and blocking gate opening. It also reduces the pool of 26S proteasomes necessary for the ubiquitin-dependent protein degradation. We demonstrate proteasome dysfunction can be prevented and reversed by proteasome agonist that lowers 20S affinity to oligomers and promotes allosteric gate opening. We show that proteasome activation with TAT-DEN prevents cognitive deficits in AD animal models. This suggests proteasome dysfunction is a key downstream target in AD pathology and supports proteasome activation as a therapeutic strategy to restore neuronal function in AD.

molecular biology↗

bioRxiv2024

Altered Proteasome Composition in Aging Brains, Genetic Proteasome Augmentation Mitigates Age-Related Cognitive Declines, and Acute Proteasome Agonist Treatment Rescues Age-Related Cognitive Deficits in Mice

The aging brain experiences a significant decline in proteasome function, The proteasome is critical for many key neuronal functions including neuronal plasticity, and memory formation/retention. Treatment with proteasome inhibitors impairs these processes. Our study reveals a marked reduction in 20S and 26S proteasome activities in aged mice brains driven by reduced functionality of aged proteasome. This is matched by a decline in 20S proteasome but an increase in 26S proteasome. Our data suggests this may be a compensatory response to reduced functionality. By overexpressing the proteasome subunit PSMB5 in the neurons of mice, enhancing proteasome function, we slowed age-related declines in spatial learning and memory as well neuromuscular declines. We then showed acute treatment with a proteasome activator to rescue spatial learning and memory deficits in aged mice. These findings highlight the potential of proteasome augmentation as a therapeutic strategy to mitigate age-related cognitive declines.

neuroscience↗

bioRxiv2024

Bacterial metabolic remodelling by convergent evolution in response to host niche-dependent nutrient availability

New pathogens often arise after host jump events between species. However, our understanding of how bacterial pathogens pivot to distinct nutrient availabilities in a new host niche is limited. Staphylococcus aureus is a multi-host pathogen responsible for a global burden of disease in humans and farmed animals. Multiple human-to-bovine host switching events led to the emergence of S. aureus as a leading cause of intramammary infection in dairy cattle. Here, we employed ex vivo milk infections to investigate how bovine S. aureus has adapted to the dairy niche revealing metabolic remodelling including upregulation of genes for lactose utilisation and branched-chain amino acid biosynthesis in response to nutrient availability. Notably, infection of milk by bovine S. aureus results in a milk clotting phenotype associated with enhanced bacterial growth that is dependent on the protease aureolysin. The same adaptive phenotype has evolved convergently in different bovine S. aureus lineages via mutations in distinct regulatory gene loci that promote enhanced aureolysin expression. Taken together, we have dissected a key adaptive trait for a bacterial pathogen after a host-switch event, involving metabolic remodelling in response to the availability of nutrients. These findings highlight the remarkable evolutionary plasticity of S. aureus underpinning its multi-host species tropism.

microbiology↗

bioRxiv2020

Population analysis of Legionella pneumophila reveals the basis of resistance to complement-mediated killing

Legionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires disease. L. pneumophila is typically a symbiont of free-living amoeba, and our understanding of the bacterial factors that determine human pathogenicity is limited. Here we carried out a population genomic study of 900 L. pneumophila isolates from human clinical and environmental samples to examine their genetic diversity, global distribution and the basis for human pathogenicity. We found that although some clones are more commonly associated with clinical infections, the capacity for human disease is representative of the breadth of species diversity. To investigate the bacterial genetic basis for human disease potential, we carried out a genome-wide association study that identified a single gene (lag-1), to be most strongly associated with clinical isolates. Molecular evolutionary analysis showed that lag-1, which encodes an O-acetyltransferase responsible for lipopolysaccharide modification, has been distributed horizontally across all major phylogenetic clades of L. pneumophila by frequent recent recombination events. Functional analysis revealed a correlation between the presence of a functional lag-1 gene and resistance to killing in human serum and bovine broncho-alveolar lavage. In addition, L. pneumophila strains that express lag-1 escaped complement-mediated phagocytosis by neutrophils. Importantly, we discovered that the expression of lag-1 confers the capacity to evade complement-mediated killing by inhibiting deposition of classical pathway molecules on the bacterial surface. In summary, our combined population and functional analyses identified L. pneumophila genetic traits linked to human disease and revealed the molecular basis for resistance to complement-mediated killing, a previously elusive trait of direct relevance to human disease pathogenicity. SignificanceLegionella pneumophila is an environmental bacterium associated with a severe pneumonia known as Legionnaires disease. A small number of L. pneumophila clones are responsible for a large proportion of human infections suggesting they have enhanced pathogenicity. Here, we employed a large-scale population analysis to investigate the evolution of human pathogenicity and identified a single gene (lag-1) that was more frequently found in clinical isolates. Functional analysis revealed that the lag-1-encoded O-acetyltransferase, involved in modification of lipopolysaccharide, conferred resistance to the classical pathway of complement in human serum. These findings solve a long-standing mystery in the field regarding L. pneumophila resistance to serum killing, revealing a novel mechanism by which L. pneumophila may avoid immune defences during infection.

microbiology↗

bioRxiv2019

Can individual and integrated water, sanitation, and handwashing interventions reduce fecal contamination in the household environment? Evidence from the WASH Benefits cluster-randomized trial in rural Kenya

Combined water, sanitation, and handwashing (WSH) interventions have the potential to reduce fecal pathogens along more transmission pathways than single interventions alone. We measured Escherichia coli levels in 3909 drinking water samples, 2691 child hand rinses, and 2422 toy ball rinses collected from households enrolled in a two-year cluster-randomized controlled trial evaluating single and combined WSH interventions. Water treatment alone reduced E. coli in drinking water, while a combined WSH intervention improved water quality by the same magnitude but did not affect levels of fecal indicator bacteria on child hands or toy balls. The failure of the WSH interventions to reduce E. coli along important child exposure pathways is consistent with the lack of a protective effect from the interventions on child diarrhea or child growth during the trial. Our results have important implications for WSH program design; the sanitation and handwashing interventions implemented in this trial should not be expected to reduce child exposure to fecal contamination in other similar settings.

microbiology↗

bioRxiv2018

Integrating water, sanitation, handwashing, and nutrition interventions to reduce child soil-transmitted helminth and Giardia infections: a cluster-randomized controlled trial in rural Kenya

Background.Helminth and protozoan infections affect >1 billion children globally. Improved water, sanitation, handwashing, and nutrition could be more sustainable control strategies for parasite infections than mass drug administration (MDA), while providing other quality of life benefits.\n\nMethods and Findings.We enrolled geographic clusters of pregnant women into a cluster-randomized controlled trial that tested six interventions: disinfecting drinking water(W), improved sanitation(S), handwashing with soap(H), combined WSH, improved nutrition(N), and combined WSHN. We assessed intervention effects on parasite infections by measuring Ascaris lumbricoides, Trichuris trichiura, hookworm, and Giardia duodenalis among individual children born to enrolled mothers and their older siblings (ClinicalTrials.gov NCT01704105). We collected stool specimens from 9077 total children in 622 clusters, including 2346 children in control, 1117 in water, 1160 in sanitation, 1141 in handwashing, 1064 in WSH, 1072 in nutrition, and 1177 in WSHN. In the control group, 23% of children were infected with Ascaris lumbricoides, 1% with Trichuris trichuria, 2% with hookworm and 39% with Giardia duodenalis. After two years of intervention exposure, Ascaris infection prevalence was 18% lower in the water treatment arm (95% confidence interval (CI) 0%, 33%), 22% lower in the WSH arm (CI 4%, 37%), and 22% lower in the WSHN arm (CI 4%, 36%) compared to control. Individual sanitation, handwashing, and nutrition did not significantly reduce Ascaris infection on their own, and integrating nutrition with WSH did not provide additional benefit. Trichuris and hookworm were rarely detected, resulting in imprecise effect estimates. No intervention reduced Giardia. Reanalysis of stool samples by quantitative polymerase chain reaction (qPCR) confirmed the reductions in Ascaris infections measured by microscopy in the WSH and WSHN groups. Lab technicians and data analysts were blinded to treatment assignment, but participants and sample collectors were not blinded. The trial was funded by the Bill & Melinda Gates Foundation and USAID.\n\nConclusions.Our results suggest integration of improved water quality, sanitation, and handwashing could contribute to sustainable control strategies for Ascaris infections, particularly in similar settings with recent or ongoing deworming programs. Water treatment alone was similarly effective to integrated WSH, providing new evidence that drinking water should be given increased attention as a transmission pathway for Ascaris.

clinical trials↗