bluuebunny/crossref_metadata_2025 huggingface dataset:
Insect communities under skyglow: diffuse night-time illuminance induces spatio-temporal shifts in movement and predation
Authors: Dyer Alexander , Ryser Remo , Brose Ulrich , Amyntas Angelos , Bodnar Nora , Boy Thomas , Franziska Bucher Solveig , Cesarz Simone , Eisenhauer Nico , Gebler Alban , Hines Jes , Kyba Christopher C. M. , Menz Myles H. M. , Rackwitz Karl , Shatwell Tom , Terlau Jördis F. , Hirt Myriam R.
Published: October 2023

Artificial light at night (ALAN) is predicted to have far-reaching consequences for natural ecosystems given its influence on organismal physiology and behaviour, species interactions and community composition. Movement and predation are fundamental ecological processes that are of critical importance to ecosystem functioning. The natural movements and foraging behaviours of nocturnal invertebrates may be particularly sensitive to the presence of ALAN. However, we still lack evidence of how these processes respond to ALAN within a community context. We assembled insect communities to quantify their movement activity and predation rates during simulated Moon cycles across a gradient of diffuse night-time illuminance including the full range of observed skyglow intensities. Using radio frequency identification, we tracked the movements of insects within a fragmented grassland Ecotron experiment. We additionally quantified predation rates using prey dummies. Our results reveal that even low-intensity skyglow causes a temporal shift in movement activity from day to night, and a spatial shift towards open habitats at night. Changes in movement activity are associated with indirect shifts in predation rates. Spatio-temporal shifts in movement and predation have important implications for ecological networks and ecosystem functioning, highlighting the disruptive potential of ALAN for global biodiversity and the provision of ecosystem services.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Light pollution of freshwater ecosystems: principles, ecological impacts and remedies
Authors: Hölker Franz , Jechow Andreas , Schroer Sibylle , Tockner Klement , Gessner Mark O.
Published: October 2023

Light pollution caused by artificial light at night (ALAN) is increasingly recognized as a major driver of global environmental change. Since emissions are rapidly growing in an urbanizing world and half of the human population lives close to a freshwater shoreline, rivers and lakes are ever more exposed to light pollution worldwide. However, although light conditions are critical to aquatic species, and freshwaters are biodiversity hotspots and vital to human well-being, only a small fraction of studies conducted on ALAN focus on these ecosystems. The effects of light pollution on freshwaters are broad and concern all levels of biodiversity. Experiments have demonstrated diverse behavioural and physiological responses of species, even at low light levels. Prominent examples are skyglow effects on diel vertical migration of zooplankton and the suppression of melatonin production in fish. However, responses vary widely among taxa, suggesting consequences for species distribution patterns, potential to create novel communities across ecosystem boundaries, and cascading effects on ecosystem functioning. Understanding, predicting and alleviating the ecological impacts of light pollution on freshwaters requires a solid consideration of the physical properties of light propagating in water and a multitude of biological responses. This knowledge is urgently needed to develop innovative lighting concepts, mitigation strategies and specifically targeted measures.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
The impacts of artificial light at night on the ecology of temperate and tropical reefs
Authors: Fobert Emily K. , Miller Colleen R. , Swearer Stephen E. , Mayer-Pinto Mariana
Published: October 2023

Despite 22% of the world's coastal regions experiencing some degree of light pollution, and biologically important artificial light at night (ALAN) reaching large portions of the seafloor (greater than 75%) near coastal developments, the impacts of ALAN on temperate and tropical reefs are still relatively unknown. Because many reef species have evolved in response to low-light nocturnal environments, consistent daily, lunar, and seasonal light cycles, and distinct light spectra, these impacts are likely to be profound. Recent studies have found ALAN can decrease reproductive success of fishes, alter predation rates of invertebrates and fishes, and impact the physiology and biochemistry of reef-building corals. In this paper, we integrate knowledge of the role of natural light in temperate and tropical reefs with a synthesis of the current literature on the impacts of ALAN on reef organisms to explore potential changes at the system level in reef communities exposed to ALAN. Specifically, we identify the direct impacts of ALAN on individual organisms and flow on effects for reef communities, and present potential scenarios where ALAN could significantly alter system-level dynamics, possibly even creating novel ecosystems. Lastly, we highlight large knowledge gaps in our understanding of the overall impact of ALAN on reef systems.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Impacts of artificial light at night on the early life history of two ecosystem engineers
Authors: Tidau Svenja , Brough Fraser T. , Gimenez Luis , Jenkins Stuart R. , Davies Thomas W.
Published: October 2023

Sessile marine invertebrates play a vital role as ecosystem engineers and in benthic–pelagic coupling. Most benthic fauna develop through larval stages and the importance of natural light cycles for larval biology and ecology is long-established. Natural light–dark cycles regulate two of the largest ocean-scale processes that are fundamental to larvae's life cycle: the timing of broadcast spawning for successful fertilization and diel vertical migration for foraging and predator avoidance. Given the reliance on light and the ecological role of larvae, surprisingly little is known about the impacts of artificial light at night (ALAN) on the early life history of habitat-forming species. We quantified ALAN impacts on larval performance (survival, growth, development) of two cosmopolitan ecosystem engineers in temperate marine ecosystems, the mussel
Mytilus edulis
and the barnacle
Austrominius modestus
. Higher ALAN irradiance reduced survival in both species (57% and 13%, respectively). ALAN effects on development and growth were small overall, and different between species, time-points and parentage. Our results show that ALAN adversely affects larval survival and reiterates the importance of paternal influence on offspring performance. ALAN impacts on the early life stages of ecosystem engineering species have implications not only for population viability but also the ecological communities that these species support.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Artificial light at night (ALAN) causes shifts in soil communities and functions
Authors: Cesarz Simone , Eisenhauer Nico , Bucher Solveig Franziska , Ciobanu Marcel , Hines Jes
Published: October 2023

Artificial light at night (ALAN) is increasing worldwide, but its effects on the soil system have not yet been investigated. We tested the influence of experimental manipulation of ALAN on two taxa of soil communities (microorganisms and soil nematodes) and three aspects of soil functioning (soil basal respiration, soil microbial biomass and carbon use efficiency) over four and a half months in a highly controlled Ecotron facility. We show that during peak plant biomass, increasing ALAN reduced plant biomass and was also associated with decreased soil water content. This further reduced soil respiration under high ALAN at peak plant biomass, but microbial communities maintained stable biomass across different levels of ALAN and times, demonstrating higher microbial carbon use efficiency under high ALAN. While ALAN did not affect microbial community structure, the abundance of plant-feeding nematodes increased and there was homogenization of nematode communities under higher levels of ALAN, indicating that soil communities may be more vulnerable to additional disturbances at high ALAN. In summary, the effects of ALAN reach into the soil system by altering soil communities and ecosystem functions, and these effects are mediated by changes in plant productivity and soil water content at peak plant biomass.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Nearby night lighting, rather than sky glow, is associated with habitat selection by a top predator in human-dominated landscapes
Authors: Barrientos Rafael , Vickers Winston , Longcore Travis , Abelson Eric S. , Dellinger Justin , Waetjen David P. , Fandos Guillermo , Shilling Fraser M.
Published: October 2023

Artificial light at night (ALAN) is increasing in extent and intensity across the globe. It has been shown to interfere with animal sensory systems, orientation and distribution, with the potential to cause significant ecological impacts. We analysed the locations of 102 mountain lions (
Puma concolor
) in a light-polluted region in California. We modelled their distribution relative to environmental and human-disturbance variables, including upward radiance (nearby lights), zenith brightness (sky glow) and natural illumination from moonlight. We found that mountain lion probability of presence was highly related to upward radiance, that is, related to lights within approximately 500 m. Despite a general pattern of avoidance of locations with high upward radiance, there were large differences in degree of avoidance among individuals. The amount of light from artificial sky glow was not influential when included together with upward radiance in the models, and illumination from moonlight was not influential at all. Our results suggest that changes in visibility associated with lunar cycles and sky glow are less important for mountain lions in their selection of light landscapes than avoiding potential interactions with humans represented by the presence of nearby lights on the ground.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Polyethylene terephthalate (PET) micro- and nanoplastic particles affect the mitochondrial efficiency of human brain vascular pericytes without inducing oxidative stress
Authors: Gettings Sean M. , Timbury William , Dmochowska Anna , Sharma Riddhi , MacKenzie Lewis E. , Miquelard-Garnier Guillaume , Bourbia Nora
Published: October 2023

The objective of this investigation was to evaluate the influence of micro- and nanoplastic particles composed of polyethylene terephthalate (PET), a significant contributor to plastic pollution, on human brain vascular pericytes. Specifically, we delved into their impact on mitochondrial functionality, oxidative stress, and the expression of genes associated with oxidative stress and ferroptosis. Our findings demonstrate that the exposure of a monoculture of human brain vascular pericytes to PET particlesin vitroat a concentration of 50 ppm for a duration of 6 days did not elicit oxidative stress. Notably, we observed an augmentation in various aspects of mitochondrial respiration, including extracellular acidification, proton pump leakage, maximal respiration, spare respiratory capacity, and ATP production in pericytes subjected to PET particles. Furthermore, there were no statistically significant alterations in mitochondrial DNA copy number, or the expression of genes linked to oxidative stress and ferroptosis.

These outcomes suggest that, at a concentration of 50 parts per million (ppm) and for 6 days exposure, PET particles do not induce oxidative stress in human brain vascular pericytes. Instead, they seem to incite a potential mitochondrial hormesis, also named mitohormesis, response, which seemingly enhances mitochondrial function. Further investigations are warranted to explore the stages of mitohormesis and the potential consequences of plastics on the integrity of the blood-brain barrier and intercellular interactions. This research contributes to our comprehension of the potential repercussions of nanoplastic pollution on human health and underscores the imperative need for ongoing examinations into the exposure to plastic particles.

Graphical Abstract (created withBioRender.com)

Highlight

Fabrication of polyethylene terephthalate (PET) micro- and nanoplastics

PET particles increase pericytes mitochondrial respiration functions

PET particles increase pericytes extracellular acidification

Oxidative stress was not observed in pericytes subjected to PET particles
High-quality genome assemblies of four members of thePodospora anserinaspecies complex
Authors: Ament-Velásquez S. Lorena , Vogan Aaron A. , Wallerman Ola , Hartmann Fanny , Gautier Valérie , Silar Philippe , Giraud Tatiana , Johannesson Hanna
Published: October 2023

The filamentous fungusPodospora anserinais a model organism used extensively in the study of molecular biology, senescence, prion biology, meiotic drive, mating-type chromosome evolution, and plant biomass degradation. It has recently been established thatP. anserinais a member of a complex of seven, closely related species. In addition toP. anserina, high-quality genomic resources are available for two of these taxa. Here we provide chromosome-level annotated assemblies of the four remaining species of the complex, as well as a comprehensive dataset of annotated assemblies from a total of 28Podosporagenomes. We find that all seven species have genomes of around 35 Mbp arranged in seven chromosomes that are mostly collinear and less than 2% divergent from each other at genic regions. We further attempt to resolve their phylogenetic relationships, finding significant levels of phylogenetic conflict as expected from a rapid and recent diversification.

Significance

Here we provide a dataset of 28 annotated genomes from theP. anserinaspecies complex, including chromosome-level assemblies of four species that lacked a reference genome. With this dataset in hand, biologists can take advantage of the molecular tools available forP. anserinato study evolutionary dynamics at the interphase between micro- and macroevolution, with particular emphasis on trait evolution, genome architecture, and speciation.
Spatial scaling of beta diversity supports the regional community concept for clades as different as ants, birds, diatoms, and trees
Authors: Ohyama Leo , Bogota-Gregory Juan D. , Jenkins David G.
Published: October 2023

Aim

Three fundamental and inter-related concepts have accrued debates: ecological communities, beta diversity (β), and spatial scale. Spatial scaling of β informs the community concept because the scale of maximal β corresponds to the most apparent size of an ecological community (without invoking external features of habitat, etc.). Here we test five alternative hypotheses about spatial scaling of β for ants, birds, diatoms, and trees across the contiguous USA, using spatial grains from 1 to 106km2. We compare β scaling among clades and test hypotheses about repeatability where data permit for: (a) summer and winter bird β in six consecutive years; (b) trees through time (4 years, spaced 5 years apart). Finally, we compare different forms of β (i.e., observed and deviations from null models based on spatial heterogeneity and spatial homogeneity).

Location

The contiguous United States of America

Time Period

Recent but varying with clade

Taxa Studied

ants, birds, diatoms, and trees

Methods

We obtained data from publicly-available sources and assigned point locations to hexagonal grids ranging from 1 to 106km2. At each spatial grain, we calculated mean pairwise β between each hexagon and its neighboring grids. We also compared alternative β measures and evaluated potential confounding effects of neighborhood size and species richness on results.

Results

Spatial scaling of β repeatedly supported the regional community concept among clades, though with different spatial scales per clade. Based on peak mean β, community size for trees (∼300 km2) < winter birds (∼500 km2) < summer birds (∼2000 km2) ≈ ants (∼2000 km2) < diatoms (∼11,000 km2). We note that community scales represent peaks on gradients rather than definitive one-size-fits-all scales. Spatial scaling of β was sensitive to seasonality (birds) and consistent among years for both birds and trees. Also, β deviation from a null model based on spatial heterogeneity adjusted observed β but was less sensitive to neighborhood size and species richness than β deviation based on spatial homogeneity.

Main conclusions

Results here indicate that: (a) similar patterns should occur across the tree of life; (b) local ecological and evolutionary forces scale up to form repeatable regional community patterns in ways not yet fully understood; (c) local biodiversity conservation efforts need to be coordinated at biogeographical scales to best achieve goals; and (d) a recent method to calculate β deviation from a null model based on spatial heterogeneity improves β research.
A novel bioinformatics pipeline for the identification of immune inhibitory receptors as potential therapeutic targets
Authors: Singh Akashdip , Bedate Alberto Miranda , von Richthofen Helen J. , Vijver Saskia V. , van der Vlist Michiel , Kuhn Raphael , Yermanos Alexander , Kuball Jurgen , Keşmir Can , Ramos M. Ines Pascoal , Meyaard Linde
Published: October 2023

Blocking inhibitory receptors like PD-1 and CTLA-4 has revolutionized cancer treatment in recent years. However, despite major successes in melanoma and lung cancer, the majority of cancer types are not responsive to these immunotherapies. As such, there is an ongoing need for the identification of novel inhibitory receptors as drug targets. Most inhibitory receptors signal via immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and previous studies have estimated that our genome contains over 1600 ITIM- bearing transmembrane proteins. However, further testing and development of this large number of candidates requires increased understanding of their expression patterns and likelihood to function as inhibitory receptor.

To assist in the selection of novel inhibitory receptor as therapeutic targets, we designed a novel bioinformatics pipeline integrating machine learning-guided structural predictions and sequence-based likelihood models to identify 51 known and 390 putative inhibitory receptors. Using publicly available transcriptomics data of immune cells, we determined the expression of these novel inhibitory receptors, and classified them into previously proposed functional categories.

Known and putative inhibitory receptors were expressed across a wide variety of immune cells, and we found cell type-specific patterns in expression of these receptors. We used our pipeline to study inhibitory receptor expression patterns in single cell transcriptomics data of tumour infiltrating T cells. We determined that putative immune inhibitory receptors were expressed differentially in CD4+and CD8+T cell subsets, including exhausted CD8+T cells and CD4+memory T cells, which could allow for subset-specific targeting.

In conclusion, we present an inhibitory receptor pipeline that identifies 51 known and 390 novel inhibitory receptors. This pipeline will support future drug target selection across diseases where therapeutic targeting of immune inhibitory receptors is warranted.
Human RAMP1 overexpressing mice are resistant to migraine therapies for motion sensitivity
Authors: Rahman Shafaqat M. , Guo Linda , Minarovich Carissa , Moon Laura , Guo Anna , Luebke Anne E.
Published: October 2023

Both enhanced motion-induced nausea and increased static imbalance are observed symptoms in migraine and especially vestibular migraine (VM). Motion-induced nausea and static imbalance were investigated in a mouse model, nestin/hRAMP1, expressing elevated levels of human RAMP1 which enhances CGRP signaling in the nervous system, and compared to non-affected littermate controls. Behavioral surrogates such as the motion- induced thermoregulation and postural sway center of pressure (CoP) assays were used to assess motion sensitivity.

Nausea readouts revealed that the nestin/hRAMP1 mouse exhibit an increased sensitivity to CGRP’s effects at lower doses compared to unaffected controls. In addition, the nestin/hRAMP1 mice exhibit a higher dynamic range in postural sway than their wildtype counterparts, along with increased sway observed in nestin/hRAMP1 male mice that was not present in male unaffected controls. Results from migraine blocker experiments were challenging to interpret, but the data suggests that olcegepant is incapable of reversing CGRP-induced or endogenous alterations in the nestin/hRAMP1 mice, while rizatriptan was ineffective in both the nestin/hRAMP1 and control mice. The results indicate that overexpression of hRAMP1 leads to heightened endogenous CGRP signaling. Results also suggest that both olcegepant and rizatriptan are ineffective in reducing nausea and sway in this hypersensitive CGRP mouse model. This study suggests that the hypersensitive nestin/hRAMP1 mouse may serve as a model for difficult to treat cases of migraine that exhibit increased motion sensitivity.
Integrative systems biology framework discovers common gene regulatory signatures in multiple mechanistically distinct inflammatory skin diseases
Authors: Mishra Bharat , Athar Mohammad , Mukhtar M. Shahid
Published: October 2023

Aim

More than 20% of the population across the world is affected by non-communicable inflammatory skin diseases including psoriasis, atopic dermatitis, hidradenitis suppurativa, rosacea, etc. Many of these chronic diseases are painful and debilitating with limited effective therapeutic interventions. However, recent advances in psoriasis treatment have improved the effectiveness and provide better management of the disease. Similar effective treatments are also needed for other chronic skin disorders regulated molecular pathogenesis. This study aims to identify common regulatory pathways and master regulators that regulate molecular pathogenesis.

Methods

We designed an integrative systems biology framework to identify the significant regulators across several inflammatory skin diseases. We exploited the gene co-expression-, and protein-protein interaction-based networks to identify shared genes and pro components in different diseases with relevant functional implications. Further, we utilized network analytics to unravel the high-priority proteins, that play a crucial role in disease pathogenesis.

Results

With conventional transcriptome analysis we identified 55 shared genes, which are enriched in several immune-associated pathways in eight inflammatory skin diseases. Our correlation-based co-expression networks identified the core co-expression networks and the integrative multi-omics interactomes providing core interactions across four of the eight diseases. Next, by implementing network analytics, we unraveled 55 high-value proteins as significant regulators in molecular pathogenesis. We believe that these significant regulators should be explored with critical experimental approaches to identify the putative drug targets for more effective treatments. As an example, we identified IKZF1 as a shared significant master regulator in three inflammatory skin diseases, which can serve as a putative drug target with known disease-derived molecules for developing efficacious combinatorial treatments for hidradenitis suppurativa, atopic dermatitis, and rosacea.

Conclusion

The conventional transcriptome results identify huge complexity among inflammatory skin diseases, which demands a systems biology perspective for comprehensive understanding. The proposed framework is very modular, which can indicate a significant path of molecular mechanism-based drug development from complex transcriptomics data and other multi-omics data.
Integrated integral population models
Authors: Portillo-Tzompa Paola , Martín-Cornejo Paulina R. , González Edgar J.
Published: October 2023

Data integration allows obtaining better descriptions and forecasting of a population’s behaviour by incorporating data at both the individual and population levels. Structured population models include the matrix population models (MPMs), which structure a population through a discrete state variable, and the integral population models (IPMs), which use a continuous variable. Two decades ago, the integrated version of MPMs appeared, but their corresponding version for IPMs is still missing.

Here, we propose the integrated integral population model (IIPM). This model takes up the ideas behind existing models used to describe and forecast the dynamics of continuously structured populations: IPMs, which use individual data, and inverse IPMs, which use population data. Particularly, we emphasise the construction and fitting of the IIPM under a Bayesian framework and use the Soay sheep database to compare the population dynamics generated by the IIPM and these existing models.

The IIPM constructed with the Soay sheep data had a good performance both at the individual (vital rates) and population (size and structure) levels, because, as they are constrained to fit both sets of data, they produce a balanced population dynamics. In turn, the IPM produced the best individual estimates and the worst population estimates, whilst the inverse IPM produced the worst individual estimates and the best population estimates.

The objective of a structured population model should be to correctly describe population patterns. IPMs, by not using population data, fail in this objective. An IIPM solves this problem.
LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension
Authors: Steppan Jochen , Wang Huilei , Nandakumar Kavitha , Poe Alan , Pak Lydia , Brady Travis , Gadkari Mahin , Berkowitz Dan E. , Shimoda Larissa A. , Santhanam Lakshmi
Published: October 2023

Background

Conduit pulmonary arterial stiffening and the resultant increase in pulmonary vascular impedance has emerged as an important underlying driver of pulmonary arterial hypertension (PAH). Given that matrix deposition is central to vascular remodeling, we evaluated the role of the collagen crosslinking enzyme lysyl oxidase like 2 (LOXL2) in this study.

Methods and Results

Human pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia showed increased LOXL2 secretion. LOXL2 activity and expression were markedly higher in primary PASMCs isolated from pulmonary arteries of the rat Sugen 5416 + hypoxia (SuHx) model of severe PH. Similarly, LOXL2 protein and mRNA levels were increased in pulmonary arteries (PA) and lungs of rats with PH (SuHx and monocrotaline (MCT) models). Pulmonary arteries (PAs) isolated from rats with PH exhibited hypercontractility to phenylephrine and attenuated vasorelaxation elicited by acetylcholine, indicating severe endothelial dysfunction. Tensile testing revealed a a significant increase in PA stiffness in PH. Treatment with PAT-1251, a novel small-molecule LOXL2 inhibitor, improved active and passive properties of the PA ex vivo. There was an improvement in right heart function as measured by right ventricular pressure volume loopsin-vivowith PAT-1251. Importantly PAT-1251 treatment ameliorated PH, resulting in improved pulmonary artery pressures, right ventricular remodeling, and survival.

Conclusion

Hypoxia induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH, as well as pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 is a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH.

New & Noteworthy

Pulmonary arterial stiffening contributes to the progression of PAH and the deterioration of right heart function. This study shows that LOXL2 is upregulated in rat models of PH. LOXL2 inhibition halts pulmonary vascular remodeling and improves PA contractility, endothelial function and improves PA pressure, resulting in prolonged survival. Thus, LOXL2 is an important mediator of PA remodeling and stiffening in PH and a promising target to improve PA pressures and survival in PH.
Machine Learning Based Identification and Characterization of Mast cells in Eosinophilic Esophagitis
Authors: Zhang Simin , Caldwell Julie M. , Rochman Mark , Collins Margaret H. , Rothenberg Marc E.
Published: October 2023

Background

Eosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis.

Objective

Using machine learning, we localized and characterized esophageal mast cells to decipher their potential role in disease pathology.

Methods

Esophageal biopsy samples (EoE, control) were stained for mast cells by anti-tryptase and imaged using immunofluorescence; high-resolution whole tissue images were digitally assembled. Machine learning software was trained to identify, enumerate, and characterize mast cells, designated Mast Cell-Artificial Intelligence (MC-AI).

Results

MC-AI enumerated cell counts with high accuracy. During active EoE, epithelial mast cells increased and lamina propria (LP) mast cells decreased. In controls and EoE remission patients, papillae had the highest mast cell density and negatively correlated with epithelial mast cell density. Mast cell density in the epithelium and papillae correlated with the degree of epithelial eosinophilic inflammation, basal zone hyperplasia, and LP fibrosis. MC-AI detected greater mast cell degranulation in the epithelium, papillae, and LP in EoE patients compared with control individuals. Mast cells were localized further from the basement membrane in active EoE than EoE remission and controls individuals but were closer than eosinophils to the basement membrane in active EoE.

Conclusion

Using MC-AI, we identified a distinct population of homeostatic esophageal papillae mast cells; during active EoE, this population decreases, undergoes degranulation, negatively correlates with epithelial mast cell levels, and significantly correlates with distinct histologic features. Overall, MC-AI provides a means to understand the potential involvement of mast cells in EoE and other disorders.

Clinical Implication

We have developed a methodology for identifying, enumerating, and characterizing mast cells using artificial intelligence; this has been applied to decipher eosinophilic esophagitis and provides a platform approach for other diseases.

Capsule Summary

A machine learning protocol for identifying mast cells, designated Mast Cell–Artificial Intelligence, readily identified spatially distinct and dynamic populations of mast cells in EoE, providing a platform to better understand this cell type in EoE and other diseases.
Neural entrainment induced by periodic audiovisual stimulation: A large-sample EEG study
Authors: Frohlich Joel , Simonian Ninette , Hanada Grant , Kothe Christian , Reggente Nicco
Published: October 2023

Stroboscopic or “flicker” stimulation is a form of periodic visual stimulation that induces geometric hallucinations through closed eyelids. While the visual effects of this form of sensory stimulation have received considerable attention, few studies have investigated the neural entrainment effects of periodic visual stimulation. Here, we introduce two variants of the classic flicker paradigm while recording EEG to study neural entrainment effects in a large sample (over 80 participants per condition). In the first condition, we used multimodal stimulation composed of two simultaneous visual strobe frequencies paired with binaural beats which provided auditory stimulation at roughly the same frequency as the slower strobe. We compared this condition to sham stimulation, in which both strobes were set to very low frequencies and in which the binaural beats were absent. Additionally, we compared both conditions to a control group in which participants focused on their breathing during eyes-closed meditation (no stimulation). Our results demonstrate powerful evidence of neural entrainment at the frequency of the slower strobe in the experimental condition. Moreover, our findings resemble effects reported in prior literature using conventional non-invasive techniques for electromagnetic brain stimulation. We argue that stroboscopic stimulation should be further developed along these lines, e.g., as a potential therapeutic technique in psychiatric disorders.
Microbubble dynamics in brain microvessels
Authors: Bezer James H. , Prentice Paul , Kee Chang William Lim , Morse Sophie V. , Christensen-Jeffries Kirsten , Rowlands Christopher J. , Kozlov Andriy S. , Choi James J.
Published: October 2023

Background

Focused ultrasound stimulation of microbubbles is being tested in clinical trials for its ability to deliver drugs across the blood-brain barrier (BBB). This technique has the potential to treat neurological diseases by preferentially delivering drugs to targeted regions. Yet despite its potential, the physical mechanisms by which microbubbles alter the BBB permeability remain unclear, as direct observations of microbubbles oscillating in cerebral capillaries have never been previously recorded.

The purpose of this study was to reveal how microbubbles respond to ultrasound when within the microvessels of living brain tissue.

Methods

Microbubbles in acute brain slices acquired from juvenile rats perfused with a concentrated solution of SonoVue® and dye were exposed to ultrasound pulses typically used in BBB disruption (center frequency: 1 MHz, peak-negative pressure: 0.2–1 MPa, pulse length: up to 10 ms) and observed using high-speed microscopy at up to 10 million frames per second.

Results

We observed that microbubbles can exert mechanical stresses on a wide region of tissue beyond their initial location and immediate surroundings. A single microbubble can apply mechanical stress to parenchymal tissues several micrometers away from the vessel. Microbubbles can travel at high velocities within the microvessels, extending their influence across tens of micrometers during a single pulse. With longer pulses and higher pressures, microbubbles could penetrate the vessel wall and move through the parenchyma, refuting a previous assumption that microbubbles are confined to vessels. The probability of extravasation scales approximately with mechanical index, being rare at low pressures, but much more common at a mechanical index ≥ 0.6.

Conclusions

These observations provide important insight into microbubble dynamics in microvessels, and are critical leads into ultimately identifying the microbubble activities that lead to both safe drug delivery and into activities we seek to avoid, such as petechiae and other bioeffects.
High-content fluorescence bioassay to investigate pore formation, ion channel modulation and cell membrane lysis induced by venoms
Authors: Kramer Simon , Kotapati Charan , Cao Yuanzhao , Fry Bryan G , Palpant Nathan J , King Glenn F , Cardoso Fernanda C
Published: October 2023

Venoms comprise highly evolved bioactive molecules modulating ion channels, receptors, coagulation factors, and the cellular membrane. This array of targets and bioactivity requires high-content bioassays to aid the development of novel envenomation treatments and biotechnological and pharmacological agents. To address this gap in venom’s research, we developed a fluorescence-based high-throughput and high-content cellular assay to simultaneously identify common cellular activities produced by venoms: membrane lysis, pore-formation, and ion channel modulation. By combining intracellular calcium with extracellular nucleic acid measurements, we distinguished these venom mechanisms using one cellular assay. We applied our high-content bioassay in three cell types exposed to venom components representing lytic, ion pore-forming or ion channel modulator toxins. Beyond the distinct profiles produced by these three types of action mechanisms, we found that the pore-forming latrotoxin α-Lt1a prefers human neuroblastoma to kidney cells and cardiomyocytes, while the lytic bee peptide melittin is not selective. Furthermore, evaluation of snake venoms showed that Elapid species induced rapid membrane lysis, while Viper species showed variable to no activity on neuroblastoma cells. These findings demonstrate that our high-content bioassay distinguish clades and interspecific traits and capture the clinical observations at venom level and is capable of differentiate ion pore-forming from membrane lysis and ion channel modulation. We hope our research will accelerate the understanding of venom biology and the diversity of toxins inducing cytotoxic, cardiotoxic and neurotoxic effects and assist in identifying venom components whose properties could benefit humankind.
Not all Bacterial Outer Membrane Proteins are β-Barrels
Authors: Heido John , Keng Simon , Kadevari Pream , Poyrazoglu Hulya , Priyam Ekta , Jayasinghe Sajith
Published: October 2023

The discovery of WzA, an octomeric helical barrel integral bacterial outer membrane protein, has challenged the widely held understanding that all integral outer membrane proteins of gram-negative bacteria are closed β-barrels composed of transmembrane β-strands. WzA is a member of the outer membrane polysaccharide exporter family and a bioinformatics analysis suggests that other members of the family may also contain outer membrane transmembrane segments that are helical. A review of the literature indicates that in addition to Wza, outer membrane core complex proteins of the type IV secretion systems also contain transmembrane segments that are helical.
Deep Learning enables reliable and comprehensive profiling of invertible promoters in microbes
Authors: Wen Jiejie , Zhang Haobo , Chu Dongliang , Chen Xiaoke , Li Yuxue , Liu Guanxi , Zhang Yuhao , Ning Kang
Published: October 2023

Invertible promoters (invertons) are regulatory elements found in bacteria, with inverted repeat sequences at both ends, leading to alternating changes in the expression of the regulated genes. Since invertons were present in more than 20% of bacterial genomes, while they regulated more than 5% of genes in these genomes, they are of pivotal importance for microbial functional dynamics especially when under stress. However, the prevalence of invertons, as well as the full spectrum of gene functions regulated by them, remain poorly understood. In this study, we developed DeepInverton, a deep learning model capable of accurately identifying novel inverton sequences without sequencing reads, which could profile inverton sequences from large genomic and metagenomic datasets. We conducted a pan-genomic and pan-metagenomic analysis of invertons on 68,969 bacterial genomes and 8,516 metagenome samples, resulting in a comprehensive overview of more than 200,000 nonredundant invertons and their regulated gene functional patterns. This result suggests that invertons, as a key player for bacterial adaptation to environmental stresses, are prevalent in bacterial genomes. Among the genomes analyzed, we observed a profound enrichment of invertons in pathogen such asBordetella pertussis, and discovered a significant increase of inverton enrichment rates in strains associated with recent pertussis outbreaks, as well as novel evolving strains, unveiling a hidden link between the evolution ofBordetella pertussisand its inverton enrichment. We also utilized DeepInverton to explore inverton profiles mong human and marine metagenomes. Results revealed an unprecedented diversity of functional genes regulated by invertons, including antimicrobial resistance, biofilm formation and flagella, indicating their potential role in facilitating environmental adaptation. Thein vitroexperiments have confirmed the functions of tens of novel invertons that we have identified. Overall, we developed the DeepInverton model for exploration of invertons at unprecedented scale, which enabled our comprehensive profiling of invertons and their regulated genes. The comprehensive inverton profiles have deepen our understanding of invertons at pan-genome and metagenome scale, and could enabled a broad spectrum of inverton-related applications in microbial ecology and synthetic biology.
Complement dysregulation is a predictive and therapeutically amenable feature of long COVID
Authors: Baillie Kirsten , Davies Helen E , Keat Samuel B K , Ladell Kristin , Miners Kelly L , Jones Samantha A , Mellou Ermioni , Toonen Erik J M , Price David A , Morgan B Paul , Zelek Wioleta M
Published: October 2023

Background

Long COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID.

Methods

We quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/gender/infection/vaccine-matched patients with long COVID.

Findings

Markers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785.

Conclusions

These findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID.

Funding

This work was funded by the National Institute for Health Research (COV-LT2-0041), the PolyBio Research Foundation, and the UK Dementia Research Institute.
A calibration protocol for soil-crop models
Authors: Wallach Daniel , Buis Samuel , Seserman Diana-Maria , Palosuo Taru , Thorburn Peter , Mielenz Henrike , Justes Eric , Kersebaum Kurt-Christian , Dumont Benjamin , Launay Marie , Seidel Sabine Julia
Published: October 2023

Process-based soil-crop models are widely used in agronomic research. They are major tools for evaluating climate change impact on crop production. Multi-model simulation studies show a wide diversity of results among models, implying that simulation results are very uncertain. A major path to improving simulation results is to propose improved calibration practices that are widely applicable. This study proposes an innovative generic calibration protocol. The two major innovations concern the treatment of multiple output variables and the choice of parameters to estimate, both of which are based on standard statistical procedure adapted to the particularities of soil-crop models. The protocol performed well in a challenging artificial-data test. The protocol is formulated so as to be applicable to a wide range of models and data sets. If widely adopted, it could substantially reduce model error and inter-model variability, and thus increase confidence in soil-crop model simulations.
A genetic screen for dominant chloroplast reactive oxygen species signaling mutants reveals life stage-specific singlet oxygen signaling networks
Authors: Lemke Matthew D. , Woodson Jesse D.
Published: October 2023

Plants employ intricate molecular mechanisms to respond to abiotic stresses, which often lead to the accumulation of reactive oxygen species (ROS) within organelles such as chloroplasts. Such ROS can produce stress signals that regulate cellular response mechanisms. One ROS, singlet oxygen (1O2), is predominantly produced in the chloroplast during photosynthesis and can trigger chloroplast degradation, programmed cell death (PCD), and retrograde (organelle-to-nucleus) signaling. However, little is known about the molecular mechanisms involved in these signaling pathways or how many different signaling1O2pathways may exist. TheArabidopsis thaliana plastid ferrochelatase two(fc2) mutant conditionally accumulates chloroplast1O2, makingfc2a valuable genetic system for studying chloroplast1O2-initiated signaling. Here, we have used activation tagging in a new forward genetic screen to identify eight dominantfc2activation-tagged (fas) mutations that suppress chloroplast1O2-initiated PCD. Whilefc2 fasmutants all block1O2-triggered PCD in the adult stage, only twofc2 fasmutants block such cellular degradation at the seedling stage, suggesting that life-stage-specific1O2-response pathways exist. In addition to PCD,fasmutations generally reduce1O2-induced retrograde signals. Furthermore,fasmutants have enhanced tolerance to excess light, a natural mechanism to produce chloroplast1O2. However, general abiotic stress tolerance was only observed in onefc2 fasmutant (fc2 fas2). Together, this suggests that plants can employ general stress tolerance mechanisms to overcome1O2production but that this screen was mostly specific to1O2signaling. We also observed that salicylic acid (SA) and jasmonate (JA) stress hormone response marker genes were induced in1O2-stressedfc2and generally reduced byfasmutations, suggesting that SA and JA signaling is correlated with active1O2signaling and PCD. Together, this work highlights the complexity of1O2signaling by demonstrating that multiple pathways may exist and introduces a suite of new1O2signaling mutants to investigate the mechanisms controlling chloroplast-initiated degradation, PCD, and retrograde signaling.