bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling the anisotropic inelastic response of polymeric scaffolds for
in situ
tissue engineering applications
Authors: Terzano Michele , Wollner Maximilian P. , Kainz Manuel P. , Rolf-Pissarczyk Malte , Götzen Nils , Holzapfel Gerhard A.
Published: September 2023

In situ
tissue engineering offers an innovative solution for replacement valves and grafts in cardiovascular medicine. In this approach, a scaffold, which can be obtained by polymer electrospinning, is implanted into the human body and then infiltrated by cells, eventually replacing the scaffold with native tissue.
In silico
simulations of the whole process in patient-specific models, including implantation, growth and degradation, are very attractive to study the factors that might influence the end result. In our research, we focused on the mechanical behaviour of the polymeric scaffold and its short-term response. Following a recently proposed constitutive model for the anisotropic inelastic behaviour of fibrous polymeric materials, we present here its numerical implementation in a finite element framework. The numerical model is developed as user material for commercial finite element software. The verification of the implementation is performed for elementary deformations. Furthermore, a parallel-plate test is proposed as a large-scale representative example, and the model is validated by comparison with experiments.
Acquired predator recognition via epidermal alarm cues but not dietary alarm cues by isolated pupfish
Authors: Wisenden Brian D. , Anderson Cody M. , Hanson Kathryn A. , Johnson Molly I. M. , Stockwell Craig A.
Published: September 2023

We tested whether Shoshone pupfish
Cyprinodon nevadensis shoshone
and Amargosa River pupfish
C. n. amargosae
respond behaviourally to conspecific chemical alarm cues released when epidermal tissue is damaged by a predator. We found that both subspecies reduced activity and vertical position in the water column in response to alarm cues. We then tested if pupfish can use alarm cue to acquire recognition of a novel predator. We trained pupfish with (1) water + odour of largemouth bass fed a diet of earthworms, (2) alarm cues from skin extract (epidermal alarm cues) + odour of bass fed a diet of earthworms, or (3) water + odour of bass fed a diet of pupfish (dietary alarm cues). Pupfish responded to epidermal alarm cues but not to dietary alarm cues. Pupfish were retested with the odour of bass that were fed an earthworm diet. Pupfish that had previously received epidermal alarm cues reduced vertical position and activity relative to the other two treatments. This is the first demonstration of acquired recognition of a novel predator by a pupfish, the first report of partial predator naiveté, and opens the possibility of predator-recognition training as a tool for management and conservation of endangered desert fishes.
Roost selection by synanthropic bats in rural Kenya: implications for human–wildlife conflict and zoonotic pathogen spillover
Authors: Jackson Reilly T. , Webala Paul W. , Ogola Joseph G. , Lunn Tamika J. , Forbes Kristian M.
Published: September 2023

Many wildlife species are synanthropic and use structures built by humans, creating a high-risk interface for human–wildlife conflict and zoonotic pathogen spillover. However, studies that investigate features of urbanizing areas that attract or repel wildlife are currently lacking. We surveyed 85 buildings used by bats and 172 neighbouring buildings unused by bats (controls) in southeastern Kenya during 2021 and 2022 and evaluated the role of microclimate and structural attributes in building selection. We identified eight bat species using buildings, with over 25% of building roosts used concurrently by multiple species. Bats selected taller cement-walled buildings with higher water vapour pressure and lower presence of permanent human occupants. However, roost selection criteria differed across the most common bat species: molossids selected structures like those identified by our main dataset whereasCardioderma corselected buildings with lower presence of permanent human occupants. Our results show that roost selection of synanthropic bat species is based on specific buildings attributes. Further, selection criteria that facilitate bat use of buildings are not homogeneous across species. These results provide information on the general mechanisms of bat–human contact in rural settings, as well as specific information on roost selection for synanthropic bats in urbanizing Africa.
Using ChatGPT for human–computer interaction research: a primer
Authors: Tabone Wilbert , de Winter Joost
Published: September 2023

ChatGPT could serve as a tool for text analysis within the field of Human–Computer Interaction, though its validity requires investigation. This study applied ChatGPT to: (1) textbox questionnaire responses on nine augmented-reality interfaces, (2) interview data from participants who experienced these interfaces in a virtual simulator, and (3) transcribed think-aloud data of participants who viewed a real painting and its replica. Using a hierarchical approach, ChatGPT produced scores or summaries of text batches, which were then aggregated. Results showed that (1) ChatGPT generated sentiment scores of the interfaces that correlated extremely strongly (r> 0.99) with human rating scale outcomes and with a rule-based sentiment analysis method (criterion validity). Additionally, (2) by inputting automatically transcribed interviews to ChatGPT, it provided meaningful meta-summaries of the qualities of the interfaces (face validity). One meta-summary analysed in depth was found to have substantial but imperfect overlap with a content analysis conducted by an independent researcher (criterion validity). Finally, (3) ChatGPT's summary of the think-aloud data highlighted subtle differences between the real painting and the replica (face validity), a distinction corresponding with a keyword analysis (criterion validity). In conclusion, our research indicates that, with appropriate precautions, ChatGPT can be used as a valid tool for analysing text data.
Equations for small amplitude shallow water waves over small bathymetric variations
Authors: Israwi Samer , Khalifeh Youssef , Mitsotakis Dimitrios
Published: September 2023

A generalized version of the

a
b
c
d

-Boussinesq class of systems is derived to accommodate variable bottom topography in two-dimensional space. This extension allows for the conservation of suitable energy functionals in some cases and enables the description of water waves in closed basins with well-justified slip–wall boundary conditions. The derived systems possess a form that ensures their solutions adhere to important principles of physics and mathematics. By demonstrating their consistency with the Euler equations and estimating their approximation error, we establish the validity of these new systems. Their derivation is based on the assumption of small bathymetric variations. With practical applications in mind, we assess the effectiveness of some of these new systems through comparisons with standard benchmarks. The results indicate that the assumptions made during the derivation are not overly restrictive. The applications of the new systems encompass a wide range of scenarios, including the study of tsunamis, tidal waves and waves in ports and lakes.
Parametric effects of light acting via multiple photoreceptors contribute to circadian entrainment in
Drosophila melanogaster
Authors: Abhilash Lakshman , Shafer Orie Thomas
Published: September 2023

Circadian rhythms in physiology and behaviour have near 24 h periodicities that must adjust to the exact 24 h geophysical cycles on earth to ensure adaptive daily timing. Such adjustment is called entrainment. One major mode of entrainment is via the continuous modulation of circadian period by the prolonged presence of light. Although
Drosophila melanogaster
is a prominent insect model of chronobiology, there is little evidence for such continuous effects of light in the species. In this study, we demonstrate that prolonged light exposure at specific times of the day shapes the daily timing of activity in flies. We also establish that continuous UV- and blue-blocked light lengthens the circadian period of
Drosophila
and provide evidence that this is produced by the combined action of multiple photoreceptors which, includes the cell-autonomous photoreceptor
cryptochrome
. Finally, we introduce ramped light cycles as an entrainment paradigm that produces light entrainment that lacks the large light-driven startle responses typically displayed by flies and requires multiple days for entrainment to shifted cycles. These features are reminiscent of entrainment in mammalian models systems and make possible new experimental approaches to understanding the mechanisms underlying entrainment in the fly.
What's in a mate? Social pairing decisions and spatial cognitive ability in food-caching mountain chickadees
Authors: Branch Carrie L. , Welklin Joseph F. , Sonnenberg Benjamin R. , Benedict Lauren M. , Heinen Virginia K. , Pitera Angela M. , Bridge Eli S. , Pravosudov Vladimir V.
Published: September 2023

While researchers have investigated mating decisions for decades, gaps remain in our understanding of how behaviour influences social mate choice. We compared spatial cognitive performance and food caching propensity within social pairs of mountain chickadees inhabiting differentially harsh winter climates to understand how these measures contribute to social mate choice. Chickadees rely on specialized spatial cognitive abilities to recover food stores and survive harsh winters, and females can discriminate among males with varying spatial cognition. Because spatial cognition and caching propensity are critical for survival and likely heritable, pairing with a mate with such enhanced traits may provide indirect benefits to offspring. Comparing the behaviour of social mates, we found that spatial cognitive performance approached a significant correlation within pairs at low, but not at high elevation. We found no correlation within pairs in spatial reversal cognitive performance at either elevation; however, females at high elevation tended to perform better than their social mates. Finally, we found that caching propensity correlated within pairs at low, while males cached significantly more food than their social mates at high elevations. These results suggest that cognition and caching propensity may influence social mating decisions, but only in certain environments and for some aspects of cognition.
Kin selection of time travel: the social evolutionary causes and consequences of dormancy
Authors: Twyman Kalyani Z. , Gardner Andy
Published: September 2023

A basic mechanism of kin selection is limited dispersal, whereby individuals remain close to their place of origin such that even indiscriminate social interaction tends to modify the fitness of genealogical kin. Accordingly, the causes and consequences of dispersal have received an enormous amount of attention in the social evolution literature. This work has focused on dispersal of individuals in space, yet similar logic should apply to dispersal of individuals in time (e.g. dormancy). We investigate how kin selection drives the evolution of dormancy and how dormancy modulates the evolution of altruism. We recover dormancy analogues of key results that have previously been given for dispersal, showing that: (1) kin selection favours dormancy as a means of relaxing competition between relatives; (2) when individuals may adjust their dormancy behaviour to local density, they are favoured to do so, resulting in greater dormancy in high-density neighbourhoods and a concomitant ‘constant non-dormant principle’; (3) when dormancy is constrained to be independent of density, there is no relationship between the rate of dormancy and the evolutionary potential for altruism; and (4) when dormancy is able to evolve in a density-dependent manner, a greater potential for altruism is expected in populations with lower dormancy.
Individual preferences for sound tool design in a parrot
Authors: Heinsohn R. , Zdenek C. N. , Appleby D. , Endler J. A.
Published: September 2023

The rarity of tool manufacture in wild parrots is surprising because they share key life-history traits with advanced tool-using species, including large brains, complex sociality and prolonged parental care. When it does occur, tool manufacture in parrots tends to be innovative, spontaneous and individually variable, but most cases have been in captivity. In the wild, only palm cockatoos (
Probosciger aterrimus
) have been observed using tools regularly. However, they are unusual because they use tools to enhance their displays rather than for foraging or self-maintenance. Males in northern Australia make two types of tool from sticks and seed pods, which they tap rhythmically against a tree during display. We analysed 256 sound tools retrieved from 70 display trees. Drumsticks (89% of tools) were used more often than seed pod tools; most males manufactured only drumsticks, but some made both types. Individual males differed significantly in the design of their drumsticks including the length, width and mass but we found no evidence that neighbours copied each other. We discuss the highly individualized preferences for sound tool design in context of the behavioural predispositions behind the rarity of tool manufacture in wild parrots.
Exploring the connection between autophagy and heat-stress tolerance in
Drosophila melanogaster
Authors: Willot Quentin , du Toit Andre , de Wet Sholto , Huisamen Elizabeth J. , Loos Ben , Terblanche John S.
Published: September 2023

Mechanisms aimed at recovering from heat-induced damages are closely associated with the ability of ectotherms to survive exposure to stressful temperatures. Autophagy, a ubiquitous stress-responsive catabolic process, has recently gained renewed attention as one of these mechanisms. By increasing the turnover of cellular structures as well as the clearance of long-lived protein and protein aggregates, the induction of autophagy has been linked to increased tolerance to a range of abiotic stressors in diverse ectothermic organisms. However, whether a link between autophagy and heat-tolerance exists in insect models remains unclear despite broad ecophysiological implications thereof. Here, we explored the putative association between autophagy and heat-tolerance using
Drosophila melanogaster
as a model. We hypothesized that (i) heat-stress would cause an increase of autophagy in flies' tissues, and (ii) rapamycin exposure would trigger a detectable autophagic response in adults and increase their heat-tolerance. In line with our hypothesis, we report that flies exposed to heat-stress present signs of protein aggregation and appear to trigger an autophagy-related homoeostatic response as a result. We further show that rapamycin feeding causes the systemic effect associated with target of rapamycin (TOR) inhibition, induces autophagy locally in the fly gut, and increases the heat-stress tolerance of individuals. These results argue in favour of a substantial contribution of autophagy to the heat-stress tolerance mechanisms of insects.
Genotype-by-environment interactions influence the composition of the
Drosophila
seminal proteome
Authors: Zeender Valérian , Pfammatter Sibylle , Roschitzki Bernd , Dorus Steve , Lüpold Stefan
Published: September 2023

Ejaculate proteins are key mediators of post-mating sexual selection and sexual conflict, as they can influence both male fertilization success and female reproductive physiology. However, the extent and sources of genetic variation and condition dependence of the ejaculate proteome are largely unknown. Such knowledge could reveal the targets and mechanisms of post-mating selection and inform about the relative costs and allocation of different ejaculate components, each with its own potential fitness consequences. Here, we used liquid chromatography coupled with tandem mass spectrometry to characterize the whole-ejaculate protein composition across 12 isogenic lines of
Drosophila melanogaster
that were reared on a high- or low-quality diet. We discovered new proteins in the transferred ejaculate and inferred their origin in the male reproductive system. We further found that the ejaculate composition was mainly determined by genotype identity and genotype-specific responses to larval diet, with no clear overall diet effect. Nutrient restriction increased proteolytic protein activity and shifted the balance between reproductive function and RNA metabolism. Our results open new avenues for exploring the intricate role of genotypes and their environment in shaping ejaculate composition, or for studying the functional dynamics and evolutionary potential of the ejaculate in its multivariate complexity.
Influence of colour vision on attention to, and impression of, complex aesthetic images
Authors: Hiramatsu Chihiro , Takashima Tatsuhiko , Sakaguchi Hiroaki , Chen Xu , Tajima Satohiro , Seno Takeharu , Kawamura Shoji
Published: September 2023

Humans exhibit colour vision variations due to genetic polymorphisms, with trichromacy being the most common, while some people are classified as dichromats. Whether genetic differences in colour vision affect the way of viewing complex images remains unknown. Here, we investigated how people with different colour vision focused their gaze on aesthetic paintings by eye-tracking while freely viewing digital rendering of paintings and assessed individual impressions through a decomposition analysis of adjective ratings for the images. Gaze-concentrated areas among trichromats were more highly correlated than those among dichromats. However, compared with the brief dichromatic experience with the simulated images, there was little effect of innate colour vision differences on impressions. These results indicate that chromatic information is instructive as a cue for guiding attention, whereas the impression of each person is generated according to their own sensory experience and normalized through one's own colour space.
Do air-breathing fish suffer branchial oxygen loss in hypoxic water?
Authors: Aaskov Magnus L. , Nelson Derek , Lauridsen Henrik , Huong Do Thi Thanh , Ishimatsu Atsushi , Crossley Dane A. , Malte Hans , Bayley Mark
Published: September 2023

In hypoxia, air-breathing fish obtain O2from the air but continue to excrete CO2into the water. Consequently, it is believed that some O2obtained by air-breathing is lost at the gills in hypoxic water.Pangasionodon hypophthalmusis an air-breathing catfish with very large gills from the Mekong River basin where it is cultured in hypoxic ponds. To understand howP. hypophthalmuscan maintain high growth in hypoxia with the presumed O2loss, we quantified respiratory gas exchange in air and water. In severe hypoxia (PO2: ≈ 1.5 mmHg), it lost a mere 4.9% of its aerial O2uptake, while maintaining aquatic CO2excretion at 91% of the total. Further, even small elevations in water PO2rapidly reduced this minor loss. Charting the cardiovascular bauplan across the branchial basket showed four ventral aortas leaving the bulbus arteriosus, with the first and second gill arches draining into the dorsal aorta while the third and fourth gill arches drain into the coeliacomesenteric artery supplying the gut and the highly trabeculated respiratory swim-bladder. Substantial flow changes across these two arterial systems from normoxic to hypoxic water were not found. We conclude that the proposed branchial oxygen loss in air-breathing fish is likely only a minor inefficiency.
Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa
Authors: Ruhal Rohit , Ghosh Moumita , Kumar Vineet , Jain Deepti
Published: September 2023

Pseudomonas aeruginosa

is an opportunistic, multidrug-resistant pathogen capable of adapting to numerous environmental conditions and causing fatal infections in immunocompromised patients. The predominant lifestyle of

P. aeruginosa

is in the form of biofilms, which are structured communities of bacteria encapsulated in a matrix containing exopolysaccharides, extracellular DNA (eDNA) and proteins. The matrix is impervious to antibiotics, rendering the bacteria tolerant to antimicrobials.

P. aeruginosa

also produces a plethora of virulence factors such as pyocyanin, rhamnolipids and lipopolysaccharides among others. In this study we present the molecular characterization of pslC and pslI genes, of the exopolysaccharide operon, that code for putative glycosyltransferases. PslC is a 303 amino acid containing putative GT2 glycosyltrasferase, whereas PslI is a 367 aa long protein, possibly functioning as a GT4 glycosyltransferase. Mutation in either of these two genes results in a significant reduction in biofilm biomass with concomitant decline in c-di-GMP levels in the bacterial cells. Moreover, mutation in pslC and pslI dramatically increased susceptibility of

P. aeruginosa

to tobramycin, colistin and ciprofloxacin. Additionally, these mutations also resulted in an increase in rhamnolipids and pyocyanin formation. We demonstrate that elevated rhamnolipids promote a swarming phenotype in the mutant strains. Together these results highlight the importance of PslC and PslI in the biogenesis of biofilms and their potential as targets for increased antibiotic susceptibility and biofilm inhibition.
Comparing methylation levels assayed in GC-rich regions with current and emerging methods
Authors: Guanzon Dominic , Ross Jason P , Ma Chenkai , Berry Oliver , Liew Yi Jin
Published: September 2023

DNA methylation is an epigenetic mechanism that regulates gene expression, and for mammals typically occurs on cytosines within CpG dinucleotides. A significant challenge for methylation detection methods is accurately measuring methylation levels within GC-rich regions such as gene promoters, as inaccuracies compromise downstream biological interpretation of the data. To address this challenge, we compared methylation levels assayed using four different methods: Enzymatic Methyl-seq (EM-seq), whole genome bisulphite sequencing (WGBS), Infinium arrays (Illumina MethylationEPIC, “EPIC”), and Oxford Nanopore Technologies nanopore sequencing (ONT) applied to human DNA. Overall, all methods produced comparable and consistent methylation readouts across the human genome. The flexibility offered by current gold standard WGBS in interrogating genome-wide cytosines is surpassed technically by both EM-seq and ONT, as their coverages and methylation readouts are less prone to GC bias. These advantages are tempered by increased laboratory time (EM-seq) and higher complexity (ONT). We further assess the strengths and weaknesses of each method, and provide recommendations in choosing the most appropriate methylation method for specific scientific questions or translational needs.
Activity-driven emergence of genealogical enclaves in growing bacterial colonies
Authors: Rani Garima , Sengupta Anupam
Published: September 2023

Bacterial dispersal, the movement of cells spanning diverse physical scales and environments, has been long investigated owing to its far-reaching ramifications in the ecology and evolution of bacterial species and their consortia. A major proportion of bacterial species are surface associated, yet if and how they disperse, specifically during the early stages of biofilm formation, remains to be understood. While physical vectors like fluid flow drive dispersal across large scales, surface-associated cells may benefit from the active biomechanical forces to navigate locally within a colony. Here, by analyzing sessile bacterial colonies, we study how cells disperse over generations due to the growth-induced forces under different conditions. A custom-built labelfree algorithm, developed to track the progeny cells as they grow and divide, reveals the emergence of distinct self-similar genealogical enclaves which intermix over time. Biological activity, indicated by the division times, is a key determinant of the intermixing dynamics; while topological defects appearing at the interface of the enclaves mediate the morphology of finger-like interfacial domains. By quantifying the Shannon entropy, we show that dividing bacterial cells have spatial affinity to close relatives, at the cost of the entropically favourable option of intermixing, wherein faster growing colonies show higher drop in the Shannon entropy over time. A coarse-grained lattice modelling of such colonies, combined with insights from the thermodynamics of phase separation, suggest that the emergence of genealogical enclaves results from an interplay of growth-induced cell dispersal within the colony (which promotes intermixing) and stochasticity of cell division, alongwith the cell-cell interactions at a given growth condition. Our study uncovers the evolution of so-far hidden emergent self-organising features within growing bacterial colonies, which while displaying a high degree of self-similarity on a range of phenotypic traits, point at competing roles of growth-induced forces and entropic landscapes which ultimately shape the genealogical distance of cells to their kith and kin within growing colonies.

One Sentence Summary

Label-free tracking of cells reveals spatio-temporal evolution of genealogical enclaves in growing bacterial colonies resulting from activity-controlled emergent demixing of cell lineages.
Ganglioside Lipids Inhibit the Aggregation of the Alzheimer’s Related Peptide Amyloid-β
Authors: Toprakcioglu Zenon , Jayaram Akhila K. , Knowles Tuomas P. J.
Published: September 2023

The aggregation of the amyloid-β(Aβ) peptides (Aβ42/Aβ40) into toxic amyloid fibrils and plaques is one of the molecular hallmarks in dementia and Alzheimers disease (AD). While the molecular mechanisms behind this aggregation process are not fully known, it has been shown that some biomolecules can accelerate this process while others can inhibit amyloid formation. Lipids, which are ubiquitously found in cell membranes, play a pivotal role in protein aggregation. Here, we investigate how ganglioside lipids, which are abundant in the brain and in neurons, can influence the aggregation kinetics of both Aβ42 and Aβ40. We find that ganglioside lipids can drastically inhibit the aggregation of Aβ42, while in the case of the smaller peptide (Aβ40), gangliosides can completely inhibit the aggregation process. Moreover, through kinetic analysis we show that the primary nucleation rate is greatly affected by the addition of gangliosides, and that the presence of these lipids can inhibit the primary nucleation rate of Aβ42 by 3 orders of magnitude. By means of viability assays of neuroblastoma cells (SH-SY5Y), we further demonstrate that amyloid fibrils formed in the absence of gangliosides are more toxic to these cells than amyloid fibrils formed in the presence of gangliosides, elucidating the inhibitory and potentially protective role that these lipids can play. Additionally, we show that monomeric Aβ40/Aβ42 form complexes with gangliosides, but not with other lipids such as POPS, suggesting that formation of ganglioside-Aβcomplexes can act as a potential pathway towards inhibiting amyloid-βaggregation. Taken together, our results provide a quantitative description of how lipid molecules such as gangliosides can inhibit the aggregation of Aβand shed light on the key factors that control these processes, especially in view of the fact that declining levels of gangliosides in neurons have been associated with ageing.
Majority of human circulating plasmablasts stop blasting: A probable misnomer
Authors: Nguyen Doan C. , Saney Celia , Hentenaar Ian T. , Cabrera-Mora Monica , Woodruff Matthew C. , Andrews Joel , Lonial Sagar , Sanz Ignacio , Lee F. Eun-Hyung
Published: September 2023

Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be “blasting” or proliferative. In this study, we find >95% nascent blood ASC in culture express Ki-67 but only 6-12% incorporate BrdU after 4h or 24h labeling. In contrast, <5% BM LLPC in culture are Ki-67+with no BrdU uptake. Due to limitations of traditional flow cytometry, we utilized a novel optofluidic technology to evaluate cell division with simultaneous functional Ig secretion. We find 11% early-minted blood ASC undergo division, and none of the terminally differentiated BM LLPC (CD19-CD38hiCD138+) divide during the 7-21 days in culture. While BM LLPC undergo complete cell cycle arrest, the process of differentiation into an ASC of plasmablasts discourages entry into S phase. Since the majority of Ki-67+nascent blood ASC have exited cell cycle and are no longer actively “blasting”, the term “plasmablast”, which traditionally refers to an ASC that still has the capacity to divide, may probably be a misnomer.
Cell4D: A general purpose spatial stochastic simulator for cellular pathways
Authors: Chan Donny , Cromar Graham L. , Taj Billy , Parkinson John
Published: September 2023

STRUCTURED ABSTRACT

Motivation

With the generation of vast compendia of ‘omics datasets, the challenge is how best to interpret these datasets to gain meaningful biological insights. Key to this challenge are computational methods that enable domain-users to generate novel hypotheses that can be used to guide future experiments. Of particular interest are flexible modeling platforms, capable of simulating a diverse range of biological systems with low barriers of adoption to those with limited computational expertise.

Results

We introduce Cell4D, a spatial-temporal modeling platform combining a robust simulation engine with integrated graphics visualization, a model design editor, and an underlying XML data model capable of capturing a variety of cellular functions. Cell4D provides an interactive visualization mode, allowing intuitive feedback on model behaviour and exploration of novel hypotheses, together with a non-graphics mode, compatible with high performance cloud compute solutions, to facilitate generation of statistical data. To demonstrate the flexibility and effectiveness of Cell4D, we investigate the dynamics of CEACAM1 localization in T-cell activation. We confirm the importance of Ca++microdomains in activating calmodulin and highlight a key role of activated calmodulin on the surface expression of CEACAM1. We further show how lymphocyte-specific protein tyrosine kinase can help regulate this cell surface expression and exploit spatial modeling features of Cell4D to test the hypothesis that lipid rafts regulate clustering of CEACAM1 to promote trans-binding to neighbouring cells. Through demonstrating its ability to test and generate hypotheses, Cell4D represents an effective tool to help interpret complex ‘omics datasets.

Availability and Implementation

https://github.com/ParkinsonLab/cell4d

Contact

jparkin@sickkids.ca
Duoculture diminishes social interaction costs and improves growth rates of two fish species at different temperatures
Authors: Yao Hong , O’Bryant Paul. , Rapp Dean. , Gao Zhe-Xia. , Wang Han-Ping
Published: September 2023

Duoculture has been reported to increase growth rates of some fishes when reared in combination, due to “shading” effects between the species. Two experiments, one involving outdoor cage-rearing in a reservoir, and the other, indoor tank-rearing, were conducted within each of three temperatures ranges (means of ∼18.0°C, ∼22.0°C and ∼26.5°C), to determine whether duoculture of bluegill (BG)Lepomis macrochirusand yellow perch (YP)Perca flavescenswould lead to improved growth relative to when the two species were reared separately. Juvenile bluegill and yellow perch were reared in triplicated groups each involving monoculture sets of 100% BG and 100% YP, and a duoculture set of 50% BG + 50% YP. Experiments in cages (Exp. 1) ran for 150 days while those in tanks ran for 126 days (Exp. 2). In Experiment 1, bluegill exhibited significantly greater (P<0.05) mean weight (P<0.05) in duoculture than in monoculture, under the high summer-like range of temperature (∼26.5°C) over most of the experiment, whereas yellow perch showed no significant difference in mean weight in duoculture versus monoculture. By the end of a 150-d experiment, bluegill in duoculture outweighed those in monoculture by 62.5%. In Experiment 2, yellow perch in duoculture grew significantly larger than in monoculture (P<0.05) under the warm thermal regime (mean of ∼22°C), while no significant differences were detected in mean weight of bluegill in monoculture versus duoculture. Yellow perch in duoculture outweighed those in monoculture by 33.1% at the end of the experiment. Yellow perch performed better in duoculture than in monoculture under the low thermal regime (mean of ∼18°C) in both experiments. A significantly greater reduction of CVwtwas observed for both bluegill and yellow perch in duoculture than in monoculture in Experiment 1, while no differences in CVwtreduction were detected for bluegill in Experiment 2. Feed conversion ratios (FCR) of bluegill and yellow perch reared in duoculture were significantly lower than for both fishes reared in monoculture in Experiment 1, while there were no significant differences in FCR among the three groups throughout most of Experiment 2. Findings indicate that duoculture of yellow perch and bluegill holds good potential to improve growth and FCR, and to reduce size variation by diminishing social interaction costs.
Assessing the potential of eDNA analysis for spawning surveys in marine environments: A case study on Japanese jack mackerel
Authors: Tsuji Satsuki , Murakami Hiroaki , Masuda Reiji
Published: September 2023

Understanding spawning ecology is important for species/population management and conservation. However, conventional surveys are often time- and labour-consuming and invasive. To address these challenges, environmental DNA (eDNA) analysis has emerged as a promising method for spawning surveys. This study investigated the spawning season and diurnal changes in eDNA concentrations targeted Japanese jack mackerel in Maizuru Bay, Japan, to assess the potential of eDNA-based spawning surveys in the marine environment. First, to estimate the spawning season, eDNA concentrations at sunset and sunrise were compared monthly for one year at three sites. As Japanese jack mackerel are nocturnal spawners, eDNA concentration will increase at night during the spawning season. A significant increase in eDNA concentration was observed between sunset and sunrise in July, suggesting that this period corresponded to the spawning season. This was confirmed by egg collection surveys using a plankton net. Second, to investigate diurnal changes in eDNA concentrations during the spawning season, time-series sampling was conducted every three hours for 24 hours in July. The results indicated that eDNA concentration showed a significant diurnal change with a peak between 9 PM and midnight, which is suggested to be their spawning time window. This study successfully estimated the spawning season of Japanese jack mackerel and demonstrated the potential of eDNA-based spawning surveys for the first time in marine environments. These surveys are expected to contribute to the advancement of this field as a new approach to overcoming traditional challenges in marine spawning surveys.

Highlights

The potential of eDNA for spawning surveys was assessed in jack mackerel.

Monthly morning and evening eDNA sampling identified spawning activity in July.

Egg surveys using a plankton net confirmed the spawning event.

Time-series sampling showed a diurnal change in eDNA concentrations in July.

eDNA analysis is thus applicable for detecting spawning in marine species.
Predictive Modeling of Clinical Trial Outcomes for Novel Drugs using Digital Twin Patient Cohorts and GenerativeAI
Authors: Chebanov Dmitrii K , Misyurin Vsevolod A
Published: September 2023

There is a problem of clinical trial failure, as each new drug should surpass the effectiveness of existing treatment regimens, which becomes increasingly challenging over time. Another significant issue is treating patients who have developed resistance to the current therapies.

Essentially, the use of drug combinations or off-label drug use, where the indication does not match the diagnosis, is akin to an experiment, as there is insufficient data on which drug or combination to use.

This work proposes an approach utilizing computer modeling of patients using gene expression and clinical data. Deep learning and generative adversarial networks are employed as modeling tools. The training data for the algorithms were sourced from publicly available databases such as TCGA and Drugbank.

The modeling is based on the hypothesis of similarity between patients, similarity between drugs, as well as the similarity between individual organs and patient tissues with cell lines, with similarity being computed mathematically. As a result, a patient model is created, where the input consists of drugs and their combinations, and the output provides survival probability values. These model data can be generated in any required quantity with generative adversarial networks (GAN) technology to create observation and control groups. Consequently, it becomes possible to simulate clinical trials, forecasting their outcomes, and, most importantly, optimizing the trial parameters to maximize the likelihood of success.
IMPALA: A Comprehensive Pipeline for Detecting and Elucidating Mechanisms of Allele Specific Expression in Cancer
Authors: Chang Glenn , Porter Vanessa L. , O’Neill Kieran , Culibrk Luka , Akbari Vahid , Marra Marco A. , Jones Steven J. M.
Published: September 2023

Allele-specific expression (ASE), where transcripts from one allele are more abundant than transcripts from the other, can arise from various genetic mechanisms and has implications for gene regulation and disease. We present IMPALA (Integrated Mapping and Profiling of Allelically-expressed Loci with Annotations), a versioned and containerized pipeline for detecting ASE in samples including cancer genomes. IMPALA leverages RNA sequencing data and, optionally, phased variant, copy number variant (CNV), allelic methylation, and mutation data to identify ASE genes and uncover underlying regulatory mechanisms. IMPALA incorporates the MBASED framework for ASE detection, and outputs a comprehensive summary table and informative figures to visualize the genomic distribution of ASE genes and their correlation with potential regulatory causes. We applied IMPALA to a cancer sample and identified thousands of genes with ASE and highlighted potential somatic events that may have influenced ASE of these genes. ASE data can be used to detect the downstream consequences of genomic alterations, which facilitates the identification of dysregulated cancer-related genes. IMPALA thus provides researchers with a powerful tool for both ASE analysis and for investigating genetic factors correlated with ASE.

Availability and implementation

IMPALA is licensed under GNU General Public License v3.0 and freely available athttps://github.com/bcgsc/IMPALAandhttps://doi.org/10.5281/zenodo.8019168with documentation and tutorial.

Contact

sjones@bcgsc.ca

Supplemental information

Supplemental materials are available at Bioinformatics online. Issue section: Gene expression
Winners and losers under past and future climate change
Authors: Thomas Anne E. , Larcombe Matthew J. , Higgins Steven I. , Trabucco Antonio , Tanentzap Andrew J.
Published: September 2023

Understanding the historical and physiological context of species’ vulnerabilities to climate change is a crucial step in predicting “winners” and “losers” under climate change. However, few studies have compared the magnitude and mechanisms of extant species’ responses to climate change in both the past and the future. By combining temporally contrasting range and niche projections, we show that range shifts in the next 50 years will need to be more extreme than in the past 6000 years to track climate niches in a large plant radiation. A new subset of physiological niche traits, particularly temperature and radiation tolerance, will be strong filters of range occupancy under anthropogenic compared with Holocene climate change. In the absence of migration, temperature niche shifts tracking the magnitude of climate change will also be required for many species to maintain their present ranges. Where range shifts occur, our results suggest that communities will be restructured differently in different habitats, with widespread range contraction in the mountains and potential latitudinal range expansion in the lowlands. Our study adds to a growing body of evidence that despite the threats posed by climate change to many species, not all species will experience unmitigated loss, and that it may be possible to predict which species are most at risk based on physiological and geographical traits.
Disease related changes in ATAC-Seq of more than 450 iPSC-derived motor neuron lines from ALS patients and controls
Authors: Tsitkov Stanislav , Valentine Kelsey , Kozareva Velina , Donde Aneesh , Frank Aaron , Lei Susan ,   the Answer ALS Consortium, Eyk Jennifer Van , Finkbeiner Steve , Rothstein Jeffrey , Thompson Leslie , Sareen Dhruv , Svendsen Clive N. , Fraenkel Ernest
Published: September 2023

Amyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured by ATAC-seq, of motor neuron cultures derived from a diverse group of 380 ALS patients and 80 healthy controls. We find that chromatin accessibility is heavily influenced by sex, the iPSC cell type of origin, ancestry, and the inherent variance arising from sequencing. Once these covariates are corrected for, we are able to identify robust ALS-specific signals in the data. Additionally, we find that the ATAC-seq data is able to predict ALS disease progression rates with similar accuracy to methods based on biomarkers and clinical status. These results suggest that iPSC-derived motor neurons recapitulate important disease-relevant epigenomic changes.
Networks of descending neurons transform command-like signals into population-based behavioral control
Authors: Braun Jonas , Hurtak Femke , Wang-Chen Sibo , Ramdya Pavan
Published: September 2023

To transform intentions into actions, movement instructions must pass from the brain to downstream motor circuits through descending neurons (DNs). These include small sets of command-like neurons that are sufficient to drive behaviors—the circuit mechanisms for which remain unclear. Here, we show that command-like DNs inDrosophiladirectly recruit networks of additional DNs to orchestrate flexible behaviors. Specifically, we found that optogenetic activation of command-like DNs previously thought to drive behaviors alone in fact co-activate larger populations of DNs. Connectome analysis revealed that this functional recruitment can be explained by direct excitatory connections between command-like DNs and networks of interconnected DNs in the brain. The size of downstream DN networks is predictive of whether descending population recruitment is necessary to generate a complete behavior: DNs with many downstream descending partners require network recruitment to drive flexible behaviors, while neurons with fewer partners can alone drive stereotyped behaviors and simple movements. Finally, DN networks reside within behavior-specific clusters that inhibit one another. These results support a mechanism for command-like descending control whereby a continuum of stereotyped to flexible behaviors are generated through the recruitment of increasingly large DN networks which likely construct a complete behavior by combining multiple motor subroutines.
Helminth ecological requirements shape the impact of climate change on the hazard of infection
Authors: Vanalli Chiara , Mari Lorenzo , Casagrandi Renato , Gatto Marino , Cattadori Isabella M.
Published: September 2023

Outbreaks and spread of infectious diseases are often associated with seasonality and changes caused by global warming. Free-living stages of soil-transmitted helminths are highly susceptible to environmental drivers, however, how multiple climatic variables affect helminth species, and the long-term consequences of these interactions, is poorly understood. We used experiments on nine trichostrongylid species to develop a temperature- and humidity-dependent model of infection hazard, which was then implemented at the European scale under climate change scenarios. Intestinal and stomach helminths exhibited contrasting climatic responses, with the former group strongly affected by temperature while the latter primarily impacted by humidity. These differences generated seasonal changes in the timing and intensity of the infection hazard and spatial heterogeneities within and between the two groups. A future range expansion of both groups toward northern latitudes is expected to create new opportunities for the co-circulation of the studied helminth species.
A large effect fitness trade-off across environments is explained by a single mutation affecting cold acclimation
Authors: Lee Gwonjin , Sanderson Brian J. , Ellis Thomas J. , Dilkes Brian P. , McKay John K. , Ågren Jon , Oakley Christopher G.
Published: September 2023

Identifying the genetic basis of local adaptation and fitness trade-offs across environments is a central goal of evolutionary biology. Cold acclimation is an adaptive plastic response for surviving seasonal freezing, and costs of acclimation may be a general mechanism for fitness trade-offs across environments in temperate zone species. Starting with locally adapted ecotypes ofArabidopsis thalianafrom Italy and Sweden, we examined the fitness consequences of a naturally occurring functional polymorphism inCBF2. This gene encodes a transcription factor that is a major regulator of cold-acclimated freezing tolerance, and resides within a locus responsible for a genetic trade-off for long-term mean fitness. We estimated the consequences of alternate genotypes ofCBF2on 5-year mean fitness and fitness components at the native field sites by comparing near isogenic lines with alternate genotypes ofCBF2to their genetic background ecotypes. The effects ofCBF2were validated at the nucleotide level using gene edited lines in the native genetic backgrounds grown in simulated parental environments. The foreignCBF2genotype in the local genetic background reduced long-term mean fitness in Sweden by more than 10%, primarily via effects on survival. In Italy, fitness was reduced by more than 20%, primarily via effects on fecundity. At both sites, the effects were temporally variable and much stronger in some years. The gene edited lines confirmed thatCBF2encodes the causal variant underlying this genetic trade-off. Additionally, we demonstrated a substantial fitness cost of cold acclimation, which has broad implications for potential maladaptive responses to climate change.