Biology subjects

Bohm, M.

Publications and source records attributed to Bohm, M..

10 recordsLinked to original sources

bioRxiv2026

In vivo experimental model of β-glucan-induced innate immune memory

SUMMARYInnate immune memory is the ability of innate immune cells to develop a recallable, epigenetically imprinted response after an initial stimulus, enabling them to mount differential responses upon restimulation. Here, we present a detailed protocol of {beta}-glucan preparation, and its in vivo application to modulate innate immune memory in mice through repeated intraperitoneal (IP) injections. This approach results in enhanced hematopoiesis and bone marrow specific myeloid bias, key hallmarks of in vivo innate immune memory responses. For complete details on the use and execution of this protocol, please refer to Hassan et al. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/705736v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@d41c3aorg.highwire.dtl.DTLVardef@18939cdorg.highwire.dtl.DTLVardef@31e879org.highwire.dtl.DTLVardef@956f6b_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIPreparation of {beta}-glucan for in vivo experiments. C_LIO_LIIn vivo modulation of innate immune memory through repeated intraperitoneal {beta}-glucan injections in mice. C_LIO_LIModulation of innate immune memory is assessed by enhanced bone marrow hematopoiesis and GMP production. C_LI

immunology↗

bioRxiv2025

Phylogenetically-informed crayfish conservation in the face of climate change

Crayfish are an ancient clade of freshwater decapods that play vital and diverse ecological roles in the freshwater systems that they inhabit. One third of assessed crayfish species are threatened with extinction and 87% are highly sensitive to climate change. However, the extent to which the evolutionary history of crayfish is threatened, especially by climate change, remains unclear. To address this, we produced a phylogenetically-informed species prioritisation for the conservation of crayfish and explored the consequences of projected climate change scenarios on crayfish phylogenetic diversity. We used the EDGE2 metric to highlight 70 priority species for conservation. Their combined threatened evolutionary history accounts for 40.7% of the expected phylogenetic diversity loss for all 673 crayfish. Of these priority species, 45.7% are vulnerable to climate change, with the majority (32 species) located in Australia. Under a high warming scenario, individual species that are more evolutionarily distinct are projected to be disproportionately affected. The extinction of climate change vulnerable species could cause the loss of up to 26.3% more phylogenetic diversity than the random expectation, equivalent to 409 million years of evolutionary history. Our results highlight the need to consider climate change effects on phylogenetic diversity to fully understand its impact on biodiversity. If actions were taken to avoid a worst-case warming scenario in favour of an intermediate scenario, we could safeguard 251 million years of unique crayfish evolutionary history.

ecology↗

bioRxiv2024

Mitochondrial reactive oxygen species cause arrhythmias in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and caused by genetic variants that often increase sarcomeric Ca2+ sensitivity. While Ca2+ sensitization explains diastolic dysfunction, the genesis of ventricular arrhythmias is unresolved. Here, we show that HCM mutations or pharmacological interventions that increase myofilament Ca2+ sensitivity generate bioenergetic mismatch and oxidative stress during {beta}-adrenergic stimulation which provide a trigger and a substrate for arrhythmias. For any given sarcomere shortening that produces work and consumes ATP, less Ca2+ stimulates the Krebs cycle to maintain mitochondrial NADH. This reverses the mitochondrial transhydrogenase to regenerate NADH from NADPH, supporting ATP production at the cost of NADPH-dependent antioxidative capacity. The ensuing overflow of reactive oxygen species (ROS) from mitochondria and glutathione oxidation induce spontaneous Ca2+ release from the sarcoplasmic reticulum and Ca2+ waves, well-defined triggers of arrhythmias. Furthermore, transhydrogenase-dependent ROS formation slows electrical conduction during {beta}-adrenergic stimulation in vivo, providing a substrate for arrhythmias. Chronic treatment with a mitochondrially-targeted ROS scavenger abolishes the arrhythmic burden during {beta}-adrenergic stimulation in HCM mice in vivo, while inducing mitochondrial ROS with a redox cycler is sufficient to induce arrhythmias in wild-type animals. These findings may lead to new strategies to prevent sudden cardiac death in patients with HCM.

physiology↗

bioRxiv2024

Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways

Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy affecting the elderly, for which therapeutic options are limited. DNA hypomethylating agents (HMAs) provide transient responses, failing to eradicate the malignant clone. Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization, evidenced by alterations in histone marks H3K9me2 and H3K9me3. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In solid cancers, the antitumor efficacy of HMAs involves the derepression of TEs, mimicking a state of viral infection. In this study, we demonstrate a significant disorganization of heterochromatin in CMML HSCs and progenitors (HSPCs) characterized by an increase in the repressive mark H3K9me2, mainly at the level of TEs, and a repression of immune and age-associated transcripts. Combining HMAs with G9A/GLP H3K9me2 methyltransferase inhibitors reactivates these pathways, selectively targeting mutated cells while preserving wild-type HSCs, thus offering new therapeutic avenues for this severe myeloid malignancy.

cancer biology↗

bioRxiv2023

How much data do we need? Reliability and data deficiency in global vertebrate biodiversity trends

Global biodiversity is facing a crisis, which must be solved through effective policies and on-the-ground conservation. But governments, NGOs, and scientists need reliable indicators to guide research, conservation actions, and policy decisions. Developing reliable indicators is challenging because the data underlying those tools is incomplete and biased. For example, the Living Planet Index tracks the changing status of global vertebrate biodiversity, but taxonomic, geographic and temporal gaps and biases are present in the aggregated data used to calculate trends. But without a basis for real-world comparison, there is no way to directly assess an indicators accuracy or reliability. Instead, a modelling approach can be used. We developed a model of trend reliability, using simulated datasets as stand-ins for the "real world", degraded samples as stand-ins for indicator datasets (e.g. the Living Planet Database), and a distance measure to quantify reliability by comparing sampled to unsampled trends. The model revealed that the proportion of species represented in the database is not always indicative of trend reliability. Important factors are the number and length of time series, as well as their mean growth rates and variance in their growth rates, both within and between time series. We found that many trends in the Living Planet Index need more data to be considered reliable, particularly trends across the global south. In general, bird trends are the most reliable, while reptile and amphibian trends are most in need of additional data. We simulated three different solutions for reducing data deficiency, and found that collating existing data (where available) is the most efficient way to improve trend reliability, and that revisiting previously-studied populations is a quick and efficient way to improve trend reliability until new long-term studies can be completed and made available.

ecology↗

bioRxiv2022

EDGE2: advancing the prioritisation of threatened evolutionary history for conservation action

The global biodiversity crisis threatens the natural world and its capacity to provide benefits to humans into the future. The conservation of evolutionary history, captured by the measure phylogenetic diversity (PD), is linked to the maintenance of these benefits and future options. The Evolutionarily Distinct and Globally Endangered (EDGE) metric has, since 2007, been used to identify species for conservation action that embody large amounts of threatened evolutionary history. In 2017, we convened a workshop to update the EDGE metric to incorporate advances in the field of phylogenetically-informed conservation. Building on that workshop, we devised the metric EDGE2, which we present here. EDGE2 uses a modular, tiered approach to provide priority rankings--and associated measures of uncertainty in both phylogenetic and extinction risk data--for all species in a clade. EDGE2 takes into account the extinction risk of closely-related species to better reflect the contribution a species is expected to make to overall PD in the future. We applied EDGE2 to the worlds mammals to identify an updated list of priority EDGE species and compare the results with the original EDGE approach. Despite similarity in the priority lists produced between EDGE and EDGE2, EDGE2 places greater priority on species with fewer close relatives on the Tree of Life. As we approach a crossroads for global biodiversity policy, EDGE2 exemplifies how academic and applied conservation biologists can collaborate to guide effective priority-setting to conserve the most irreplaceable components of biodiversity upon which humanity depends.

zoology↗

bioRxiv2022

A user-friendly guide to using distance measures to compare time series in ecology.

O_LITime series are a critical component of ecological analysis, used to track changes in biotic and abiotic variables. Information can be extracted from the properties of time series for tasks such as classification, clustering, prediction, and anomaly detection. These common tasks in ecological research rely on the notion of (dis-) similarity which can be determined by using distance measures. A plethora of distance measures have been described in the scientific literature, but many of them have not been introduced to ecologists. Furthermore, little is known about how to select appropriate distance measures and the properties they focus on for time-series related tasks. C_LIO_LIHere we describe 16 potentially desirable properties of distance measures, test 42 distance measures for each property, and present an objective method to select appropriate distance measures for any task and ecological dataset. We then demonstrate our selection method by applying it to a set of real-world data on breeding bird populations in the UK. We also discuss ways to overcome some of the difficulties involved in using distance measures to compare time series. C_LIO_LIOur real-world population trends exhibit a common challenge for time series comparison: a high level of stochasticity. We demonstrate two different ways of overcoming this challenge, first by selecting distance measures with properties that make them well-suited to comparing noisy time series, and second by applying a smoothing algorithm before selecting appropriate distance measures. In both cases, the distance measures chosen through our selection method are not only fit-for-purpose but are consistent in their rankings of the population trends. C_LIO_LIThe results of our study should lead to an improved understanding of, and greater scope for, the use of distance measures for comparing time series within ecology, and allow for the answering of new ecological questions. C_LI

ecology↗

bioRxiv2021

β-glucan-induced innate immune memory distinctively affects macrophage activation in response to differential environmental cues

In vitro, exposure of human primary monocytes to the fungal {beta}-glucan enhances their pro-inflammatory responsiveness towards several pathogens. Yet, the role of environmental condition of this process remains unclear. Here we found that {beta}-glucan-induced innate immune memory counteract the anti-inflammatory status of the macrophages. In response to {beta}-glucan imprinting, M-CSF-(M2-like-) macrophages increase their pro-inflammatory responsiveness to secondary stimuli associated with decrease of the M-CSF differentiation hallmarks. In contrast, in GM-CSF-(M1-like-) environment, {beta}-glucan imprinting reduced the pro-inflammatory canonical feature of the macrophages, together with their terminal differentiation marks. Comparing M-CSF and GM-CSF environment, we observed that {beta}-glucan-imprinted macrophages present comparable functions in terms of cytokine responses, phagocytosis, oxidative burst, and angiogenesis. This effect is mediated through Dectin-1 and associated with altered expression of the master regulators of macrophage terminal differentiation, IRF5 and IRF3. {beta}-glucan-induced innate immune memory skews the commitment of the macrophages in complex environment towards similar and less terminally differentiated cells. Together, these observations suggest a potential therapeutic role for {beta}-glucan-induced modulation of innate memory in different pathological contexts.

immunology↗

bioRxiv2020

Prevalence of sustainable and unsustainable use of wild species inferred from the IUCN Red List

Unsustainable exploitation of wild species represents a serious threat to biodiversity and to the livelihoods of local communities and indigenous peoples. However, managed, sustainable use has the potential to forestall extinctions, aid recovery, and meet human needs. Research to date has focused on unsustainable biological resource use with little consideration of sustainable use; we infer the current prevalence of both. We analyzed species-level data for 30,923 species from 13 taxonomic groups on the IUCN Red List. Our results demonstrate the broad taxonomic prevalence of use, with 40% of species (10,098 of 25,009 species from 10 data-sufficient taxonomic groups) documented as being used. The main purposes of use are pets, display animals and horticulture, and human consumption. Use often has an adverse impact on species extinction risk (we define this as biologically unsustainable): intentional use is currently contributing to elevated extinction risk for over a quarter of all threatened or Near Threatened (NT) species (2,752 - 2,848 of 9,753 species). Intentional use also threatens 16% of all species used (1,597 - 1,631 of 10,098). However, 72% of species that are used (7,291 of 10,098) are Least Concern (LC), of which nearly half (3,469) also have stable or improving population trends. The remainder of used species are not documented as threatened by biological resource use, including 172 threatened or NT species with stable or improving populations. Around a third of species that have use documented as a threat do not currently receive targeted species management actions to directly address this threat. We offer suggestions for improving use-related Red List data. Our findings on the prevalence of sustainable and unsustainable use, and variation across taxa, can inform international policymaking, including the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, the Convention on Biological Diversity, and the Convention on International Trade in Endangered Species.

ecology↗

bioRxiv2019

Global priorities for conservation of reptilian phylogenetic diversity in the face of human impacts

Phylogenetic Diversity (PD) is increasingly recognised as an important measure that can provide information on evolutionary and functional aspects of biodiversity for conservation planning that are not readily captured by species diversity. Here we develop and analyse two new metrics that combine the effects of PD and human encroachment on species range size -- one metric valuing regions and another enabling species prioritisation. We evaluate these metrics for reptiles, which have been largely neglected in previous studies, and contrast these results with equivalent calculations for all terrestrial vertebrate groups. We find that high human impacted areas unfortunately coincide with the most valuable areas of reptilian diversity, more than expected by chance. We also find that, under our species-level metric, the highest priority reptile species score far above the top mammal and bird species, and they include a disproportionate number of species with insufficient information on potential threats. Such Data Deficient species are, in terms of our metric, comparable to Critically Endangered species and may require urgent conservation attention.

ecology↗