bluuebunny/crossref_metadata_2025 huggingface dataset:
A geometric framework for reaction enumeration in computational nucleic acid devices
Authors: Kumar Sarika , Lakin Matthew R.
Published: November 2023

Cascades of DNA strand displacement reactions enable the design of potentially large circuits with complex behaviour. Computational modelling of such systems is desirable to enable rapid design and analysis. In previous work, the expressive power of graph theory was used to enumerate reactions implementing strand displacement across a wide range of complex structures. However, coping with the rich variety of possible graph-based structures required enumeration rules with complicated side-conditions. This paper presents an alternative approach to tackle the problem of enumerating reactions at domain level involving complex structures by integrating with a geometric constraint solving algorithm. The rule sets from previous work are simplified by replacing side-conditions with a general check on the geometric plausibility of structures generated by the enumeration algorithm. This produces a highly general geometric framework for reaction enumeration. Here, we instantiate this framework to solve geometric constraints by a structure sampling approach in which we randomly generate sets of coordinates and check whether they satisfy all the constraints. We demonstrate this system by applying it to examples from the literature where molecular geometry plays an important role, including DNA hairpin and remote toehold reactions. This work therefore enables integration of reaction enumeration and structural modelling.
Elephants and algorithms: a review of the current and future role of AI in elephant monitoring
Authors: Brickson Leandra , Zhang Libby , Vollrath Fritz , Douglas-Hamilton Iain , Titus Alexander J.
Published: November 2023

Artificial intelligence (AI) and machine learning (ML) present revolutionary opportunities to enhance our understanding of animal behaviour and conservation strategies. Using elephants, a crucial species in Africa and Asia’s protected areas, as our focal point, we delve into the role of AI and ML in their conservation. Given the increasing amounts of data gathered from a variety of sensors like cameras, microphones, geophones, drones and satellites, the challenge lies in managing and interpreting this vast data. New AI and ML techniques offer solutions to streamline this process, helping us extract vital information that might otherwise be overlooked. This paper focuses on the different AI-driven monitoring methods and their potential for improving elephant conservation. Collaborative efforts between AI experts and ecological researchers are essential in leveraging these innovative technologies for enhanced wildlife conservation, setting a precedent for numerous other species.
A systems-level analysis of the mutually antagonistic roles of RKIP and BACH1 in dynamics of cancer cell plasticity
Authors: Shyam Sai , Ramu Soundharya , Sehgal Manas , Jolly Mohit Kumar
Published: November 2023

Epithelial–mesenchymal transition (EMT) is an important axis of phenotypic plasticity—a hallmark of cancer metastasis. Raf kinase-B inhibitor protein (RKIP) and BTB and CNC homology 1 (BACH1) are reported to influence EMT. In breast cancer, they act antagonistically, but the exact nature of their roles in mediating EMT and associated other axes of plasticity remains unclear. Here, analysing transcriptomic data, we reveal their antagonistic trends in a pan-cancer manner in terms of association with EMT, metabolic reprogramming and immune evasion via PD-L1. Next, we developed and simulated a mechanism-based gene regulatory network that captures how RKIP and BACH1 engage in feedback loops with drivers of EMT and stemness. We found that RKIP and BACH1 belong to two antagonistic ‘teams’ of players—while BACH1 belonged to the one driving pro-EMT, stem-like and therapy-resistant cell states, RKIP belonged to the one enabling pro-epithelial, less stem-like and therapy-sensitive phenotypes. Finally, we observed that low RKIP levels and upregulated BACH1 levels associated with worse clinical outcomes in many cancer types. Together, our systems-level analysis indicates that the emergent dynamics of underlying regulatory network enable the antagonistic patterns of RKIP and BACH1 with various axes of cancer cell plasticity, and with patient survival data.
Cortex-driven cytoplasmic flows in elongated cells: fluid mechanics and application to nuclear transport in
Drosophila
embryos
Authors: Htet Pyae Hein , Lauga Eric
Published: November 2023

The
Drosophila melanogaster
embryo, an elongated multi-nucleated cell, is a classical model system for eukaryotic development and morphogenesis. Recent work has shown that bulk cytoplasmic flows, driven by cortical contractions along the walls of the embryo, enable the uniform spreading of nuclei along the anterior–posterior axis necessary for proper embryonic development. Here, we propose two mathematical models to characterize cytoplasmic flows driven by tangential cortical contractions in elongated cells. Assuming Newtonian fluid flow at low Reynolds number in a spheroidal cell, we first compute the flow field exactly, thereby bypassing the need for numerical computations. We then apply our results to recent experiments on nuclear transport in cell cycles 4–6 of
Drosophila
embryo development. By fitting the cortical contractions in our model to measurements, we reveal that experimental cortical flows enable near-optimal axial spreading of nuclei. A second mathematical approach, applicable to general elongated cell geometries, exploits a long-wavelength approximation to produce an even simpler solution, with errors below

5
%

compared with the full model. An application of this long-wavelength result to transport leads to fully analytical solutions for the nuclear concentration that capture the essential physics of the system, including optimal axial spreading of nuclei.
The making of early modern eye models
Authors: Zhao Wenrui
Published: November 2023

Anatomical eye models became increasingly popular in the seventeenth century across Europe. They served as useful pedagogical tools, allowing the hands-on study of ocular anatomy and repeated re-enactment of the dissection process, while also being appreciated for their workmanship and aesthetics. Their makers included surgeons, anatomists and artisans, and they often collaborated to produce these artefacts. Comprising materials such as ivory, horn, glass and leather, the components of the model aimed to recreate and stand in for bodily surfaces and textures. This article takes the materiality of the eye model as the starting point from which to explore the role of material-based expertise and insights in producing knowledge of the body. The model encapsulated a conceptualization shared across surgical and artisanal practices that the body was a kind of material, equivalent to the matter craftsmen worked with. It enabled engagement with the body as material and encouraged a re-evaluation of sensory literacy, fostering a way of seeing that also entailed touching.
Food availability leads to more connected contact networks among peridomestic zoonotic reservoir hosts
Authors: Kuenzi Amy J. , Luis Angela D.
Published: November 2023

The North American deermouse (
Peromyscus maniculatus
) is a reservoir host for many zoonotic pathogens. Deermice have been well studied, but few studies have attempted to understand social interactions within the species despite these interactions being key to understanding disease transmission. We performed an experiment to determine if supplemental food or nesting material affected social interactions of deermice and tested if interactions increased with increasing population density. We constructed three simulated buildings that received one of three treatments: food, nesting material, or control. Mice were tagged with passive integrated transponder (PIT) tags, and their movement in and out of buildings was monitored with PIT tag readers. PIT tag readings were used to create contact networks, assuming a contact if two deermice were in the same building at the same time. We found that buildings with food led to contact networks that were approximately 10 times more connected than buildings with nesting material or control buildings. We also saw a significant effect of population density on the average number of contacts per individual. These results suggest that food supplementation which is common in peridomestic settings, can significantly increase contacts between reservoir hosts, potentially leading to increased transmission of zoonotic viruses within the reservoir host and from reservoir hosts to humans.
Can comets deliver prebiotic molecules to rocky exoplanets?
Authors: Anslow R. J. , Bonsor A. , Rimmer P. B.
Published: November 2023

In this work, we consider the potential of cometary impacts to deliver complex organic molecules and the prebiotic building blocks required for life to rocky exoplanets. Numerical experiments have demonstrated that for these molecules to survive, impacts at very low velocities are required. This work shows that for comets scattered from beyond the snow-line into the habitable zone, the minimum impact velocity is always lower for planets orbiting Solar-type stars than M-dwarfs. Using both an analytical model and numerical N-body simulations, we show that the lowest velocity impacts occur onto planets in tightly packed planetary systems around high-mass (i.e. Solar-mass) stars, enabling the intact delivery of complex organic molecules. Impacts onto planets around low-mass stars are found to be very sensitive to the planetary architecture, with the survival of complex prebiotic molecules potentially impossible in loosely packed systems. Rocky planets around M-dwarfs also suffer significantly more high velocity impacts, potentially posing unique challenges for life on these planets. In the scenario that cometary delivery is important for the origins of life, this study predicts the presence of biosignatures will be correlated with (i) decreasing planetary mass (i.e. escape velocity), (ii) increasing stellar-mass and (iii) decreasing planetary separation (i.e. exoplanets in tightly-packed systems).
Sturm–Liouville systems for the survival probability in first-passage time problems
Authors: Dahlenburg Marcus , Pagnini Gianni
Published: November 2023

We derive a Sturm–Liouville system of equations for the exact calculation of the survival probability in first-passage time problems. This system is the one associated with the Wiener–Hopf integral equation obtained from the theory of random walks. The derived approach is an alternative to the existing literature and we tested it against direct calculations from both discrete- and continuous-time random walks in a manageable, but meaningful, example. Within this framework, the Sparre Andersen theorem results to be a boundary condition for the system.
A positive effect of cumulative intergroup threat on reproductive success
Authors: Morris-Drake Amy , Cobb Benjamin , Kern Julie M. , Radford Andrew N.
Published: November 2023

Outgroup conflict is a powerful selective force across all social taxa. While it is well documented that individual outgroup contests can have a range of direct and indirect fitness consequences, the cumulative pressure of outgroup threats could also potentially impact reproductive success. Here, we use long-term life-history data from a wild population of dwarf mongooses (
Helogale parvula
) to investigate how intergroup interaction (IGI) rate might influence breeding and offspring survival. IGI rate did not predict the number of litters produced in a season or the inter-litter interval. Unexpectedly, IGI rate was positively associated with the number of pups alive three months after emergence from the breeding burrow. This was not due to a difference in how many pups emerged but because those in groups experiencing more IGIs had a higher survival likelihood post-emergence. Detailed natural observations revealed that both IGI occurrence and the threat of intergroup conflict led to more sentinel behaviour by adults, probably reducing the predation risk to young. Our results contrast the previously documented negative effects of outgroup interactions on reproductive success and highlight the need to assess cumulative threat, rather than just the impact of physical contests, when considering outgroup conflict as a social driver of fitness.
Convergence of gut microbiota in myrmecophagous amphibians
Authors: Brunetti Andrés E. , Lyra Mariana L. , Monteiro Juliane P. C. , Zurano Juan P. , Baldo Diego , Haddad Celio F. B. , Moeller Andrew H.
Published: November 2023

The gut microbiome composition of terrestrial vertebrates is known to converge in response to common specialized dietary strategies, like leaf-eating (folivory) or ant- and termite-eating (myrmecophagy). To date, such convergence has been studied in mammals and birds, but has been neglected in amphibians. Here, we analysed 15 anuran species (frogs and toads) representing five Neotropical families and demonstrated the compositional convergence of the gut microbiomes of distantly related myrmecophagous species. Specifically, we found that the gut microbial communities of bufonids and microhylids, which have independently evolved myrmecophagy, were significantly more similar than expected based on their hosts' evolutionary divergence. Conversely, we found that gut microbiome composition was significantly associated with host evolutionary history in some cases. For instance, the microbiome composition of
Xenohyla truncata
, one of the few known amphibians that eat fruits, was not different from those of closely related tree frogs with an arthropod generalist diet. Bacterial taxa overrepresented in myrmecophagous species relative to other host families include
Paludibacter
,
Treponema
, and Rikenellaceae, suggesting diet-mediated selection and prey-to-predator transmission likely driving the observed compositional convergence. This study provides a basis for examining the roles of the gut microbiome in host tolerance and sequestration of toxic alkaloids from ants and termites.
Mycoplasma phocimorsus sp. nov., isolated from Scandinavian patients with seal finger or septic arthritis after contact with seals
Authors: Skafte-Holm Axel , Pedersen Thomas Roland , Frølund Maria , Stegger Marc , Qvortrup Klaus , Michaels Dina L. , Brown Daniel R. , Jensen Jorgen Skov
Published: November 2023

Seal finger (sealer’s finger, spekk finger), an extremely painful hand infection contracted by individuals handling seals, has previously been associated with Mycoplasma phocacerebrale. From 2000 to 2014, six independent strains of a novel Mycoplasma species were isolated at Statens Serum Institut, Denmark, from Scandinavian patients with seal finger (M5725T, M6447, M6620, M6642 and M6879) or septic arthritis (M6921). Prior to the onset of infection, all patients had reported contact with unspeciated seals. All isolates grew within 2–5 days in Friis’ modified broth and metabolized glucose and arginine but not urea. Strains M5725T, M6447, M6642 and M6921 also grew in Hayflick-type media. Colonies on agar media were large (0.5–1.0 mm) and had a typical ‘fried egg’ appearance, reduced tetrazolium, and were digitonin sensitive. Growth occurred at 32 °C but not at 42 °C. Strains were susceptible to doxycycline and moxifloxacin but resistant to azithromycin and erythromycin. The genomes of the six strains were sequenced and relatedness to all known Mycoplasma species was inferred. Phylogenetic analyses using 16S rRNA gene sequences and core genome single nucleotide polymorphisms showed that the isolated strains were highly similar and phylogenetically distinct from all other species within the genus Mycoplasma. The sizes of the genome sequences of the strains ranged from 744 321 to 772409 bp, with a G+C content of 25.0–25.2 mol%. Based on these analyses, we propose a novel species of the genus Mycoplasma with the name Mycoplasma phocimorsus sp. nov. with the first isolate M5725T (NCTC 14922T=DSM 116188T) as the proposed type strain and representative strains M6447, M6620, M6642, M6879 and M6921.
Little Evidence for Homoeologous Gene Conversion and Homoeologous Exchange Events inGossypiumAllopolyploids
Authors: Conover Justin L , Grover Corrinne E , Sharbrough Joel , Sloan Daniel B , Peterson Daniel G , Wendel Jonathan F
Published: November 2023

A complicating factor in analyzing allopolyploid genomes is the possibility of physical interactions between homoeologous chromosomes during meiosis, resulting in either crossover (homoeologous exchanges) or non-crossover products (homoeologous gene conversion). This latter process was first described in cotton by comparing SNP patterns in sequences from two diploid progenitors with those from the allopolyploid subgenomes. These analyses, however, did not explicitly account for autapomorphic SNPs that may lead to similar patterns as homoeologous gene conversion, creating uncertainties about the reality of the inferred gene conversion events. Here, we use an expanded phylogenetic sampling of high-quality genome assemblies from seven allopolyploidGossypiumspecies (all derived from the same polyploidy event), four diploid species (two closely related to each subgenome), and a diploid outgroup to derive a robust method for identifying potential genomic regions of gene conversion and homoeologous exchange. Using this new method, we find little evidence for homoeologous gene conversion in allopolyploid cottons and that only two of the forty best-supported events are shared by more than one species. We do, however, reveal a single, shared homoeologous exchange event at one end of chromosome 1, which occurred shortly after allopolyploidization but prior to divergence of the descendant species. Overall, our analyses demonstrate that homoeologous gene conversion and homoeologous exchanges are uncommon inGossypium, affecting between zero and 24 genes per subgenome (0.0 - 0.065%) across the seven species. More generally, we highlight the potential problems of using simple four-taxon tests to investigate patterns of homoeologous gene conversion in established allopolyploids.

SIGNIFICANCE STATEMENT

Allopolyploidy is a prominent process in plant diversification, involving the union of two divergent genomes in a single nucleus via interspecific hybridization and genome doubling. The merger of genomes sets in motion a variety of inter-genomic and epigenomic interactions that are thought to lead to the origin of new phenotypes. Among these is recombinational exchange between duplicated chromosomes, which can involve sequence lengths ranging from several bases to entire chromosome arms, and which can be either reciprocal or unidirectional in their effects. Here we present a new analytical framework for detecting these inter-genomic recombinational processes in allopolyploids, and demonstrate that they have been rare in a group of allopolyploid species in the cotton genus.
Benchmarking kinship estimation tools for ancient genomes using pedigree simulations
Authors: Aktürk Şevval , Mapelli Igor , Güler Merve Nur , Gürün Kanat , Katırcıoğlu Büşra , Vural Kıvılcım Başak , Sağlıcan Ekin , Çetin Mehmet , Yaka Reyhan , Sürer Elif , Atağ Gözde , Çokoğlu Sevim Seda , Sevkar Arda , Altınışık N. Ezgi , Koptekin Dilek , Somel Mehmet
Published: November 2023

There is growing interest in uncovering genetic kinship patterns in past societies using low-coverage paleogenomes. Here, we benchmark four tools for kinship estimation with such data: lcMLkin, NgsRelate, KIN, and READ, which differ in their input, IBD-estimation methods and statistical approaches. We used pedigree and ancient genome sequence simulations to evaluate these tools when only a limited number (1K to 50K) of shared SNPs (with minor allele frequency ≥0.01) are available. The performance of all four tools was comparable using ≥20K SNPs. We found that first-degree related pairs can be accurately classified even with 1K SNPs, with 85% F1 scores using READ and 96% using NgsRelate or lcMLkin. Distinguishing third-degree relatives from unrelated pairs or second-degree relatives was also possible with high accuracy (F1 >90%) with 5K SNPs using NgsRelate and lcMLkin, while READ and KIN showed lower success (69% and 79%, respectively). Meanwhile, noise in population allele frequencies and inbreeding (first cousin mating) led to deviations in kinship coefficients, with different sensitivities across tools. We conclude that using multiple tools in parallel might be an effective approach to achieve robust estimates on ultra-low coverage genomes.
Lipid metabolism drives allele-specific early-stage hypertrophic cardiomyopathy
Authors: Vaniya Arpana , Karlstaedt Anja , Gulkok Damla Ates , Thottakara Tilo , Liu Yamin , Fan Sili , Eades Hannah , Fukunaga Ryuya , Vernon Hilary J. , Fiehn Oliver , Roselle Abraham M.
Published: November 2023

Hypertrophic cardiomyopathy (HCM) results from pathogenic variants in sarcomeric protein genes, that increase myocyte energy demand and lead to cardiac hypertrophy. But it is unknown whether a common metabolic trait underlies the cardiac phenotype at early disease stage. This study characterized two HCM mouse models (R92W-TnT, R403Q-MyHC) that demonstrate differences in mitochondrial function at early disease stage. Using a combination of cardiac phenotyping, transcriptomics, mass spectrometry-based metabolomics and computational modeling, we discovered allele-specific differences in cardiac structure/function and metabolic changes. TnT-mutant hearts had impaired energy substrate metabolism and increased phospholipid remodeling compared to MyHC-mutants. TnT-mutants showed increased incorporation of saturated fatty acid residues into ceramides, cardiolipin, and increased lipid peroxidation, that could underlie allele-specific differences in mitochondrial function and cardiomyopathy.

Graphical Abstract
Biomechanical filtering supports tactile encoding efficiency in the human hand
Authors: Tummala Neeli , Reardon Gregory , Dandu Bharat , Shao Yitian , Saal Hannes P. , Visell Yon
Published: November 2023

Touching an object elicits skin oscillations that are biomechanically transmitted throughout the hand, driving responses in thousands of tactile receptors, including numerous exquisitely sensitive Pacinian corpuscles (PCs). Accepted descriptions of PC functionality characterize their response properties as highly stereotyped, based on experimental data gathered when stimuli are applied near the receptor. However, during natural touch, spiking activity in the majority of PCs is evoked by transmitted skin oscillations that are modified by biomechanical filtering. This filtering mechanism, stemming from dispersive wave dynamics in the skin, bears some similarity to the pre-neuronal filtering of auditory signals by the basilar membrane, a mechanical process that is instrumental to perception. Thus, we sought to clarify how skin biomechanics might influence tactile information encoding in the periphery. We used vibrometry imaging and computational neural experiments to examine the influence of biomechanical filtering on neural activity in whole-hand PC populations. We observed complex, location- and frequency-dependent patterns of filtering that were shaped by tissue mechanics and hand morphology. This source of biomechanical modulation diversified PC population spiking activity and enhanced tactile information encoding efficiency. These findings indicate that biomechanics furnishes a pre-neuronal mechanism that facilitates efficient tactile encoding and processing.
Wintering, rather than breeding, oceanic conditions may modulate declining survival in a long-distance migratory seabird
Authors: Snell Katherine R. S. , Santos Inês Alexandre Machado dos , van Bemmelen Rob SA , Moe Børge , Thorup Kasper
Published: November 2023

Steep declines in Arctic skua populations in the southern extent of their breeding range have been reported during the last half of the 20thcentury. We used 24 years of ringing and re-encounter data from the Faroe Islands, North Atlantic, to investigate if patterns in survival probabilities can be explained by large scale climatic events. Having first determined the migratory phenology and wintering regions, we estimated the effects on survival of the North Atlantic Oscillation (NAO) index during breeding and Oceanic Niño index (ONI) during the non-breeding period within a capture-mark-recapture framework. Temporal trends, and direct and time-lagged effects of the environment on annual survival were modelled. We found support for a substantial decrease in adult annual survival, from ca. 0.93 in 1985 to ca. 0.77 in 2008, and weak support for a decrease in young (1styear) survival over the duration of the study period. Furthermore, models indicated increased young survival following an El Niño winter. We suggest this time-lagged effect reflects downstream propagation of environmental conditions, particularly food availability, or a potential carry-over effect of El Niño conditions positively impacting the performance of the parents in the subsequent breeding season, leading to improved young survival prospects. While adult mortality cannot be attributed to the oceanic climate oscillations tested here; the negative trend in survival may account for the substantial population declines observed over the last decades.
Spatial Metabolomics co-registered with Multiplex Phenotyping for the Evaluation of Human Kidney Tissue
Authors: Zickuhr Greice M , Um In Hwa , Laird Alexander , Harrison David J , Dickson Alison L
Published: November 2023

A workflow has been evaluated that utilises a single tissue section to obtain spatially co-registered, molecular, and phenotypical information suitable for AI-enabled analysis. The impact of varying DESI-MSI conditions (e.g., temperature, scan rate, acquisition time) on the detection of small molecules and on tissue quality for integration into typical clinical pathology workflows assessed in human kidney.
A multiscale approach to investigate fluorescence and NDVI imaging as proxy of photosynthetic traits in wheat
Authors: Virlet Nicolas , Pennacchi João Paulo , Sadeghi-Tehran Pouria , Ashfield Tom , Orr Douglas J. , Carmo-Silva Elizabete , Hawkesford Malcolm J.
Published: November 2023

With the development of the digital phenotyping, repeated measurements of agronomic traits over time are easily accessible, notably for morphological and phenological traits. However high throughput methods for estimating physiological traits such as photosynthesis are lacking. This study demonstrates the links of fluorescence and reflectance imaging with photosynthetic traits. Two wheat cultivars were grown in pots in a controlled environment. Photosynthesis was characterised by gas-exchange and biochemical analysis at five time points, from booting to 21 days post anthesis. On the same days imaging was performed on the same pots, at leaf and plant scale, using indoor and outdoor phenotyping platforms, respectively. Five image variables (Fv/Fmand NDVI at the whole plant level and Fv/Fm, Φ(II)532and Φ(NPQ)1077at the leaf scale) were compared to variables from A-Ci and A-Par curves, biochemical analysis, and fluorescence instruments. The results suggested that the image variables are robust estimators of photosynthetic traits, as long as senescence is driving the variability. Despite contrasting cultivar behaviour, linear regression models which account for the cultivar and the interaction effects, further improved the modelling of photosynthesis indicators. Finally, the results highlight the challenge of discriminating functional to cosmetic stay green genotypes using digital imaging.

Highlight

A temporal and multi-scale study of fluorescence and NDVI imaging used as a proxy for photosynthetic parameters
Levetiracetam Modulates Brain Metabolic Networks and Transcriptomic Signatures in the 5XFAD Mouse Model of Alzheimer’s disease
Authors: Burton Charles P. , Chumin Evgeny J. , Collins Alyssa Y. , Persohn Scott A. , Onos Kristen D. , Pandey Ravi S. , Quinney Sara K. , Territo Paul R.
Published: November 2023

INTRODUCTION

Subcritical epileptiform activity is associated with impaired cognitive function and is commonly seen in patients with Alzheimer’s disease (AD). The anti-convulsant, levetiracetam (LEV), is currently being evaluated in clinical trials for its ability to reduce epileptiform activity and improve cognitive function in AD. The purpose of the current study was to apply pharmacokinetics (PK), network analysis of medical imaging, gene transcriptomics, and PK/PD modeling to a cohort of amyloidogenic mice to establish how LEV restores or drives alterations in the brain networks of mice in a dose-dependent basis using the rigorous preclinical pipeline of the MODEL-AD Preclinical Testing Core.

METHODS

Chronic LEV was administered to 5XFAD mice of both sexes for 3 months based on allometrically scaled clinical dose levels from PK models. Data collection and analysis consisted of a multi-modal approach utilizing18F-FDG PET/MRI imaging and analysis, transcriptomic analyses, and PK/PD modeling.

RESULTS

Pharmacokinetics of LEV showed a sex and dose dependence in Cmax, CL/F, and AUC0-∞, with simulations used to estimate dose regimens. Chronic dosing at 10, 30, and 56 mg/kg, showed18F-FDG specific regional differences in brain uptake, and in whole brain covariance measures such as clustering coefficient, degree, network density, and connection strength (i.e. positive and negative). In addition, transcriptomic analysis via nanoString showed dose-dependent changes in gene expression in pathways consistent18F-FDG uptake and network changes, and PK/PD modeling showed a concentration dependence for key genes, but not for network covariance modeling.

DISCUSSION

This study represents the first report detailing the relationships of metabolic covariance and transcriptomic network changes resulting from LEV administration in 5XFAD mice. Overall, our results highlight non-linear kinetics based on dose and sex, where gene expression analysis demonstrated LEV dose- and concentration-dependent changes, along with cerebral metabolism, and/or cerebral homeostatic mechanisms relevant to human AD, which aligned closely with network covariance analysis of18F-FDG images. Collectively, this study show cases the value of a multimodal connectomic, transcriptomic, and pharmacokinetic approach to further investigate dose dependent relationships in preclinical studies, with translational value towards informing clinical study design.
Communicating information about the psychology of a wild carnivore, the red fox, influences perceived attitudinal changes but not overall tolerance in people
Authors: Morton F. Blake , Henri Dom , Adaway Kristy A. , Soulsbury Carl D. , Hopkins Charlotte R.
Published: November 2023

Studies on wild animal psychology are growing in popularity due to the important role they play in understanding how wildlife is responding to human-driven environmental changes. However, communicating psychological information to the general public could undermine specific conservation objectives by encouraging greater persecution of a species (e.g., “bold” predators). Through a national-level survey (n = 1,364 participants), we tested whether communicating information about the boldness and problem-solving abilities of a wild carnivore, the red fox (Vulpes vulpes), influences people’s tolerance of them. Half of participants were given information on fox psychology (either a video or a press release about fox boldness and problem-solving), the other half were given content related to animal ecology (either a video or a press release about fox habitat use). Afterwards, all participants completed the same 24-item questionnaire evaluating their tolerance of foxes. Although the participants given information about fox psychology were more likely to report aperceivedattitude change due to the content they were given, their attitudes relating to fox tolerance remained unaffected regardless of content or format. We encourage further research to understand how communicating different types of information might influence, either positively or negatively, people’s tolerance of a species as more studies on wild animal psychology are published, and the public’s awareness of how animal psychology relates to human-wildlife interactions becomes more widespread.

Highlights

Studies on wild animal psychology are growing in popularity

The impact of animal psychology research on public attitudes is unclear

We tested if fox psychology research influences public tolerance

People given fox psychology information reported greater attitude change

This perceived change did not impact people’s overall tolerance of foxes
Hierarchizing multi-scale environmental effects on agricultural pest population dynamics: a case study on the annual onset ofBactrocera dorsalispopulation growth in Senegalese orchards
Authors: Caumette Cécile , Diatta Paterne , Piry Sylvain , Chapuis Marie-Pierre , Faye Emile , Sigrist Fabio , Martin Olivier , Papaïx Julien , Brévault Thierry , Berthier Karine
Published: November 2023

Implementing integrated pest management programs to limit agricultural pest damage requires an understanding of the interactions between the environmental variability and population demographic processes. However, identifying key environmental drivers of spatio-temporal pest population dynamics remains challenging as numerous candidate factors can operate at a range of scales, from the field (e.g. agricultural practices) to the regional scale (e.g. weather variability). In such a context, data-driven approaches applied to pre-existing data may allow identifying patterns, correlations, and trends that may not be apparent through more restricted hypothesis-driven studies. The resulting insights can lead to the generation of novel hypotheses and inform future experimental work focusing on a limited and relevant set of environmental predictors. In this study, we developed an ecoinformatics approach to unravel the multi-scale environmental conditions that lead to the early re-infestation of mango orchards by a major pest in Senegal, the oriental fruit flyBactrocera dorsalis(BD). We gathered abundance data from a three-year monitoring conducted in 69 mango orchards as well as environmental data (i.e. orchard management, landscape structure and weather variability) across a range of spatial scales. We then developed a flexible analysis pipeline centred on a recent machine learning algorithm, which allows the combination of gradient boosting and grouped random effects models or Gaussian processes, to hierarchize the effects of multi-scale environmental variables on the onset of annual BD population growth in orchards. We found that physical factors (humidity, temperature), and to some extent landscape variables, were the main drivers of the spatio-temporal variability of the onset of population growth in orchards. These results suggest that favourable microclimate conditions could provide refuges for small BD populations that could survive, with little or no reproduction, during the mango off-season and, then, recolonize neighbouring orchards at the beginning of the next mango season. Confirmation of such a hypothesis could help to prioritize surveillance and preventive control actions in refuge areas.
Time is Confidence: Monetary Incentives Metacognitive Profile on Duration Judgment
Authors: Sarabi Mitra Taghizadeh , Zimmermann Eckart
Published: November 2023

The question we addressed in the current study is whether the mere prospect of monetary reward affects subjective time perception. To test this question, we collected trail-based confidence reports in a task in which subjects made categorical decisions about probe durations relative to the reference duration. When there was a potential to gain monetary reward, the duration was perceived to be longer than in the neutral condition, and confidence, which reflects the perceived probability of being correct, was higher in the reward condition than in the neutral condition. We found that confidence influences the sense of time in different individuals: subjects with high-confidence reported that they perceived the duration signaled by the monetary gain condition as longer than subjects with low-confidence. Our results showed that only high-confidence individuals overestimated the monetary gain context. Finally, we found a negative relationship between confidence and time perception, and that confidence bias at the maximum uncertainty duration of 450 ms is predictive of time perception. Taken together, the current study demonstrates that subjective measure of the confidence profile caused overestimation of time rather than by the outcome valence of reward expectancy.
Gene flow from Fraxinus cultivars into natural stands of Fraxinus pennsylvanica occurs range-wide, is regionally extensive, and is associated with a loss of allele richness
Authors: Abhainn Everett A. , Shirley Devin L. , Stanley Robert K. , Scarpato Tatum , Koch Jennifer L. , Romero-Severson Jeanne
Published: November 2023

In North America, the ubiquitous planting of a comparatively small number ofFraxinus(ash) cultivars in both urban and rural environments over the last 70-80 years may have permitted extensive gene flow into naturally regenerated stands. In the light of multiple biotic threats to the North AmericanFraxinus, an assessment of the extent of gene flow from ash cultivars and the current state of genetic diversity inF. pennsylvanica(green ash), one of the most widely distributed species, is needed to inform seed collection strategies for the preservation of genetic diversity range-wide. We used 16 EST-SSR markers to genotype 1291 trees from 48 naturally regenerated populations of green ash across the native range, 19F. pennsylvanicacultivars and oneF. americana(white ash) cultivar. We detected first generation cultivar parentage with high confidence in 172 individuals in 34 of the 48 populations and extensive cultivar parentage (23-50%) in eight populations. The incidence of cultivar parentage was negatively associated with allele richness (R2= 0.151, p = 0.006). The high frequency of cultivar propagule dispersal in our study suggests that a significant proportion of the standing genetic variation in local populations may not be of local origin, a result that has serious implications for the study of adaptive variation and the conservation of theFraxinusgene pool.
Quantitative Cross-Species Comparison of Serum Albumin Binding of Per- and Polyfluoroalkyl Substances from Five Structural Classes
Authors: Starnes Hannah M. , Jackson Thomas W. , Rock Kylie D. , Belcher Scott M.
Published: November 2023

Per- and polyfluoroalkyl substances (PFAS) are a class of over 8,000 chemicals that are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput,in vitrodifferential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this differential scanning fluorimetry assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H,1H,2H,2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of serum albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and perfluoroalkyl ether congeners bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive toxicity assessments for PFAS.
Dynamic co-expression modular network analysis of bHLH transcription factors regulation in the potato spindle tuber viroid-tomato pathosystem
Authors: Aviña-Padilla Katia , Zambada-Moreno Octavio , Jimenez-Limas Marco A. , Hammond Rosemarie W. , Hernández-Rosales Maribel
Published: November 2023

Viroids, minimalist plant pathogens, present significant threats to crops by causing severe diseases. The use of high-throughput sequencing technologies for analyzing the transcriptomes of viroid-infected host plants has yielded informative information on gene regulation by these pathogens, however a complete understanding of the transcriptome data suffers from the inclusion of numerous genes of unknown function. Co-expression analysis addresses this by clustering genes into modules based on global gene expression levels. Our previous study emphasized basic helix-loop-helix protein (bHLH) transcriptional reprogramming in tomato in response to different potato spindle tuber viroid (PSTVd) strains. In the current research, we delve into tissue-specific gene modules, particularly in root and leaf tissues, governed by bHLH transcription factors during PSTVd infections. Utilizing public datasets that span Control (C; (mock-inoculated), PSTVd-mild (M), and PSTVd-severe (S23) strains in time-course infections, we uncovered differentially expressed gene modules. These modules were functionally characterized, identifying essential hub genes. We identified the roles of bHLH transcription factors (TFs) in managing processes like photosynthesis and rapid membrane repair in infected roots. In leaves, external layer alterations influenced photosynthesis, linking bHLH TFs to distinct metabolic functions. Expanding on these findings, we explored bipartite networks, discerning both common and unique bHLH TF regulatory roles, notably highlighting the bifan motif’s significance in these interactions. Through this holistic approach, we deepen our understanding of viroid-host interactions and the intricate regulatory mechanisms underpinning them.
Acetylcholine Promotes Directionally Biased Glutamatergic Retinal Waves
Authors: Zhang Kathy , Su Ashley , Wang Yixiang , Crair Michael
Published: November 2023

Spontaneous retinal waves are a critical driving force for the self-organization of the mouse visual system prior to eye-opening. Classically characterized as taking place in three distinct stages defined by their primary excitatory drive, Stage II waves during the first postnatal week are propagated through the volume transmission of acetylcholine while Stage III retinal waves during the second postnatal week depend on glutamatergic transmission from bipolar cells. However, both late Stage II and early Stage III retinal waves share a defining propagation bias toward the temporal-to-nasal direction despite developmental changes in the underlying cholinergic and glutamatergic retinal networks. Here, we leverage genetic and pharmacological manipulations to investigate the relationship between cholinergic and glutamatergic neurotransmission during the transition between Stage II and Stage III wavesin vivo.We find that the cholinergic network continues to play a vital role in the propagation of waves during Stage III after the primary mode of neurotransmission changes to glutamate. In the absence of glutamatergic waves, compensatory cholinergic activity persists but lacks the propagation bias typically observed in Stage III waves. In the absence of cholinergic waves, gap junction-mediated activity typically associated with Stage I waves persists throughout the developmental window in which Stage III waves usually emerge and lacks the spatiotemporal profile of normal Stage III waves, including a temporal-to-nasal propagation bias. Finally, we show that cholinergic signaling through β2 subunit-containing nicotinic acetylcholine receptors, essential for Stage II wave propagation, is also critical for Stage III wave directionality.
GO2Sum: Generating Human Readable Functional Summary of Proteins from GO Terms
Authors: Giri Swagarika Jaharlal , Ibtehaz Nabil , Kihara Daisuke
Published: November 2023

Understanding the biological functions of proteins is of fundamental importance in modern biology. To represent function of proteins, Gene Ontology (GO), a controlled vocabulary, is frequently used, because it is easy to handle by computer programs avoiding open-ended text interpretation. Particularly, the majority of current protein function prediction methods rely on GO terms. However, the extensive list of GO terms that describe a protein function can pose challenges for biologists when it comes to interpretation. In response to this issue, we developed GO2Sum (Gene Ontology terms Summarizer), a model that takes a set of GO terms as input and generates a human-readable summary using the T5 large language model. GO2Sum was developed by fine-tuning T5 on GO term assignments and free-text function descriptions for UniProt entries, enabling it to recreate function descriptions by concatenating GO term descriptions. Our results demonstrated that GO2Sum significantly outperforms the original T5 model that was trained on the entire web corpus in generating Function, Subunit Structure, and Pathway paragraphs for UniProt entries.
Multiplexed 3D Analysis of Immune States and Niches in Human Tissue
Authors: Yapp Clarence , Nirmal Ajit J. , Zhou Felix , Maliga Zoltan , Tefft Juliann B. , Llopis Paula Montero , Murphy George F. , Lian Christine G. , Danuser Gaudenz , Santagata Sandro , Sorger Peter K.
Published: November 2023

Tissue homeostasis and the emergence of disease are controlled by changes in the proportions of resident and recruited cells, their organization into cellular neighbourhoods, and their interactions with acellular tissue components. Highly multiplexed tissue profiling (spatial omics)1makes it possible to study this microenvironmentin situ, usually in 4-5 micron thick sections (the standard histopathology format)2. Microscopy-based tissue profiling is commonly performed at a resolution sufficient to determine cell types but not to detect subtle morphological features associated with cytoskeletal reorganisation, juxtracrine signalling, or membrane trafficking3. Here we describe a high-resolution 3D imaging approach able to characterize a wide variety of organelles and structures at sub-micron scale while simultaneously quantifying millimetre-scale spatial features. This approach combines cyclic immunofluorescence (CyCIF) imaging4of over 50 markers with confocal microscopy of archival human tissue thick enough (30-40 microns) to fully encompass two or more layers of intact cells. 3D imaging of entire cell volumes substantially improves the accuracy of cell phenotyping and allows cell proximity to be scored using plasma membrane apposition, not just nuclear position. In pre-invasive melanomain situ5, precise phenotyping shows that adjacent melanocytic cells are plastic in state and participate in tightly localised niches of interferon signalling near sites of initial invasion into the underlying dermis. In this and metastatic melanoma, mature and precursor T cells engage in an unexpectedly diverse array of juxtracrine and membrane-membrane interactions as well as looser “neighbourhood” associations6whose morphologies reveal functional states. These data provide new insight into the transitions occurring during early tumour formation and immunoediting and demonstrate the potential for phenotyping of tissues at a level of detail previously restricted to cultured cells and organoids.