bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple and complex, sexually dimorphic retinal mosaic of fritillary butterflies
Authors: Ilić Marko , Chen Pei-Ju , Pirih Primož , Meglič Andrej , Prevc Jošt , Yago Masaya , Belušič Gregor , Arikawa Kentaro
Published: September 2022

Butterflies have variable sets of spectral photoreceptors that underlie colour vision. The photoreceptor organization may be optimized for the detection of body coloration. Fritillaries (Argynnini) are nymphalid butterflies exhibiting varying degrees of sexual dimorphism in wing coloration. In two sister species, the females have orange (
Argynnis paphia
) and dark wings (
Argynnis sagana
), respectively, while the males of both species have orange wings with large patches of pheromone-producing androconia. In spite of the differences in female coloration, the eyes of both species exhibit an identical sexual dimorphism. The female eyeshine is uniform yellow, while the males have a complex retinal mosaic with yellow and red-reflecting ommatidia. We found the basic set of ultraviolet-, blue- and green-peaking photoreceptors in both sexes. Males additionally have three more photoreceptor classes, peaking in green, yellow and red, respectively. The latter is the basal R9, indirectly measured through hyperpolarizations in the green-peaking R1-2. In many nymphalid tribes, including the closely related Heliconiini, the retinal mosaic is complex in both sexes. We hypothesize that the simple mosaic of female Argynnini is a secondary reduction, possibly driven by the use of olfaction for intraspecific recognition, whereas vision remains the primary sense for the task in the males.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Motion-sensitive neurons activated by chromatic contrast in a butterfly visual system
Authors: Céchetto Clément , Arikawa Kentaro , Kinoshita Michiyo
Published: September 2022

A pattern of two equally bright colours contains only chromatic contrast. Unlike in flies, such a pattern elicits strong optokinetic responses in the butterfly
Papilio xuthus
. To investigate the neural basis of chromatic motion vision, we performed single-cell electrophysiology. We found spiking neurons exhibiting direction-selective motion sensitivity in the second optic ganglion, the medulla. We analysed the response characteristics of these neurons using two-colour stripe patterns moving vertically. We systematically manipulated the intensities of the colours so that the set of presented patterns included an isoluminant condition for the butterfly. Moving patterns containing only chromatic contrast still elicited a response in the neurons. The neurons' sensitivity profile is similar to that of the behavioural responses. Post-recording dye injection revealed that the neurons have dendrites in the ventral lateral protocerebrum and axonal processes in the medulla, suggesting a feedback role. Presumably, the neurons contribute to subtracting wide-field motion to facilitate the detection of small moving targets.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Colour vision in stomatopod crustaceans
Authors: Cronin Thomas W. , Porter Megan L. , Bok Michael J. , Caldwell Roy L. , Marshall Justin
Published: September 2022

The stomatopod crustaceans, or mantis shrimps, are colourful marine invertebrate predators. Their unusual compound eyes have dorsal and ventral regions resembling typical crustacean apposition designs separated by a unique region called the midband that consists of from two to six parallel rows of ommatidia. In species with six-row midbands, the dorsal four rows are themselves uniquely specialized for colour analysis. Rhabdoms of ommatidia in these rows are longitudinally divided into three distinct regions: an apical ultraviolet (UV) receptor, a shorter-wavelength middle tier receptor and a longer-wavelength proximal tier receptor. Each of the total of 12 photoreceptors has a different spectral sensitivity, potentially contributing to a colour-vision system with 12 channels. Mantis shrimps can discriminate both human-visible and UV colours, but with limited precision compared to other colour-vision systems. Here, we review the structure and function of stomatopod colour vision, examining the types of receptors present in a species, the spectral tuning of photoreceptors both within and across species, the neural analysis of colour and the genetics underlying the multiple visual pigments used for colour vision. Even today, after many decades of research into the colour vision of stomatopods, much of its operation and its use in nature remain a mystery.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Molecular advances to study the function, evolution and spectral tuning of arthropod visual opsins
Authors: Liénard Marjorie A. , Valencia-Montoya Wendy A. , Pierce Naomi E.
Published: September 2022

Visual opsins of vertebrates and invertebrates diversified independently and converged to detect ultraviolet to long wavelengths (LW) of green or red light. In both groups, colour vision largely derives from opsin number, expression patterns and changes in amino acids interacting with the chromophore. Functional insights regarding invertebrate opsin evolution have lagged behind those for vertebrates because of the disparity in genomic resources and the lack of robust
in vitro
systems to characterize spectral sensitivities. Here, we review bioinformatic approaches to identify and model functional variation in opsins as well as recently developed assays to measure spectral phenotypes. In particular, we discuss how transgenic lines, cAMP-spectroscopy and sensitive heterologous expression platforms are starting to decouple genotype–phenotype relationships of LW opsins to complement the classical physiological-behavioural-phylogenetic toolbox of invertebrate visual sensory studies. We illustrate the use of one heterologous method by characterizing novel LW Gq opsins from 10 species, including diurnal and nocturnal Lepidoptera, a terrestrial dragonfly and an aquatic crustacean, expressing them in HEK293T cells, and showing that their maximum absorbance spectra (
λ
max
) range from 518 to 611 nm. We discuss the advantages of molecular approaches for arthropods with complications such as restricted availability, lateral filters, specialized photochemistry and/or electrophysiological constraints.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Exploiting colour space geometry for visual stimulus design across animals
Authors: Christenson Matthias P. , Mousavi S. Navid , Oriol Elie , Heath Sarah L. , Behnia Rudy
Published: September 2022

Colour vision represents a vital aspect of perception that ultimately enables a wide variety of species to thrive in the natural world. However, unified methods for constructing chromatic visual stimuli in a laboratory setting are lacking. Here, we present stimulus design methods and an accompanying programming package to efficiently probe the colour space of any species in which the photoreceptor spectral sensitivities are known. Our hardware-agnostic approach incorporates photoreceptor models within the framework of the principle of univariance. This enables experimenters to identify the most effective way to combine multiple light sources to create desired distributions of light, and thus easily construct relevant stimuli for mapping the colour space of an organism. We include methodology to handle uncertainty of photoreceptor spectral sensitivity as well as to optimally reconstruct hyperspectral images given recent hardware advances. Our methods support broad applications in colour vision science and provide a framework for uniform stimulus designs across experimental systems.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Colour vision in thrips (Thysanoptera)
Authors: Lopez-Reyes Karla , Armstrong Karen F. , van Tol Robert W. H. M. , Teulon David A. J. , Bok Michael J.
Published: September 2022

Insects are an astonishingly successful and diverse group, occupying the gamut of habitats and lifestyle niches. They represent the vast majority of described species and total terrestrial animal biomass on the planet. Their success is in part owed to their sophisticated visual systems, including colour vision, which drive a variety of complex behaviours. However, the majority of research on insect vision has focused on only a few model organisms including flies, honeybees and butterflies. Especially understudied are phytophagous insects, such as diminutive thrips (Thysanoptera), in spite of their damage to agriculture. Thrips display robust yet variable colour-specific responses despite their miniaturized eyes, but little is known about the physiological and ecological basis of their visual systems. Here, we review the known visual behavioural information about thrips and the few physiological studies regarding their eyes. Eye structure, spectral sensitivity, opsin genes and the presence of putative colour filters in certain ommatidia strongly imply dynamic visual capabilities. Finally, we discuss the major gaps in knowledge that remain for a better understanding of the visual system of thrips and why bridging these gaps is important for expanding new possibilities for applied pest management strategies for these tiny insects.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
A model for colour preference behaviour of spring migrant aphids
Authors: Döring Thomas F. , Kirchner Sascha M.
Published: September 2022

Aphids are economically and ecologically important herbivorous insects. A critical step in their life cycle is the visually guided host finding behaviour. To elucidate the role of colour in host finding of aphid spring migrants we conducted large colour trap experiments in the field and analysed aphid catch data, using trap spectral reflectance data as input. Based on known and putative photoreceptor sensitivities we developed and optimized a simple empirical colour choice model for spring migrants of different aphid species which confirmed and explained the yellow preference of these insects. In a further step, we applied multivariate statistical methods to behavioural and reflectance data, but without data on photoreceptor sensitivities, to find the wavelengths of greatest importance for the aphids' behavioural responses. This analysis confirmed the position of the green photoreceptor peak previously obtained independently with electrophysiological methods. In a final step, we applied the colour preference model to a dataset of leaf spectra. This showed that aphid visual preference would be dependent on the plants’ nutritional status, with lower nitrogen input being associated with stronger preference, despite known benefits of high nitrogen levels for aphid reproduction and fitness. Ecological and evolutionary implications of these results are discussed.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
The role of colour patterns for the recognition of flowers by bees
Authors: Hempel de Ibarra Natalie , Holtze Susanne , Bäucker Cornelia , Sprau Philipp , Vorobyev Misha
Published: September 2022

Bees discriminate between many different colours of flower petals, but it is not well understood how they perceive and learn patterns frequently found in flowers with colourful structures. We used multi-spectral imaging to explore chromatic cues in concentric flower patterns as they are seen through the low-resolution eyes of the honeybee. We find a diversity of colour combinations, which suggests that plants might exploit the sensory capabilities of pollinators, like bees, that learn colours easily. A consistent feature is that the surround of the pattern has a stronger chromatic contrast to the foliage background than the centre. This can potentially facilitate the fast identification of floral objects within colourful scenes when a foraging bee moves through a flower patch. In behavioural experiments we trained and tested bees with three types of concentric patterns. They recognized and discriminated patterns accurately in most tests, relying flexibly on both chromatic and spatial cues. Only rarely, depending on the training stimulus, chromatic cues determined their choices whilst pattern cues were ignored. The variability of floral designs and the bees' flexibility in recalling colour and spatial information suggest a role for colour vision in pattern processing. Implications for the signalling strategies of flowers are discussed.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Colour vision in nocturnal insects
Authors: Warrant Eric , Somanathan Hema
Published: September 2022

The ability to see colour at night is known only from a handful of animals. First discovered in the elephant hawk moth
Deilephila elpenor
, nocturnal colour vision is now known from two other species of hawk moths, a single species of carpenter bee, a nocturnal gecko and two species of anurans. The reason for this rarity—particularly in vertebrates—is the immense challenge of achieving a sufficient visual signal-to-noise ratio to support colour discrimination in dim light. Although no less challenging for nocturnal insects, unique optical and neural adaptations permit reliable colour vision and colour constancy even in starlight. Using the well-studied
Deilephila elpenor
, we describe the visual light environment at night, the visual challenges that this environment imposes and the adaptations that have evolved to overcome them. We also explain the advantages of colour vision for nocturnal insects and its usefulness in discriminating night-opening flowers. Colour vision is probably widespread in nocturnal insects, particularly pollinators, where it is likely crucial for nocturnal pollination. This relatively poorly understood but vital ecosystem service is threatened from increasingly abundant and spectrally abnormal sources of anthropogenic light pollution, which can disrupt colour vision and thus the discrimination and pollination of flowers.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Understanding insect colour constancy
Authors: Werner Annette
Published: September 2022

Colour constancy is the ability to recognize the colour of objects despite spectral changes in the natural illumination. As such, this phenomenon is important for most organisms with good colour vision, and it has been intensively studied in humans and primates. Colour constancy is also documented for several species of insects, which is not surprising given the ecological importance of colour vision. But how do insects, with their small brains, solve the complex problem of colour vision and colour constancy? In an interspecies approach, this review reports on behavioural studies on colour constancy in bees, butterflies, moths and humans, corresponding computational models and possible neurophysiological correlates.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Mechanisms of spectral orientation in a diurnal dung beetle
Authors: Yilmaz Ayse , el Jundi Basil , Belušič Gregor , Byrne Marcus , Baird Emily , Dacke Marie
Published: September 2022

Ball rolling dung beetles use a wide range of cues to steer themselves along a fixed bearing, including the spectral gradient of scattered skylight that spans the sky. Here, we define the spectral sensitivity of the diurnal dung beetle
Kheper lamarcki
and use the information to explore the orientation performance under a range of spectral light combinations. We find that, when presented with spectrally diverse stimuli, the beetles primarily orient to the apparent brightness differences as perceived by their green photoreceptors. Under certain wavelength combinations, they also rely on spectral information to guide their movements, but the brightness and spectral directional information is never fully disentangled. Overall, our results suggest the use of a dichromatic, primitive colour vision system for the extraction of directional information from the celestial spectral gradient to support straight-line orientation.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Insect opsins and evo-devo: what have we learned in 25 years?
Authors: McCulloch Kyle J. , Macias-Muñoz Aide , Briscoe Adriana D.
Published: September 2022

The visual pigments known as opsins are the primary molecular basis for colour vision in animals. Insects are among the most diverse of animal groups and their visual systems reflect a variety of life histories. The study of insect opsins in the fruit fly
Drosophila melanogaster
has led to major advances in the fields of neuroscience, development and evolution. In the last 25 years, research in
D. melanogaster
has improved our understanding of opsin genotype–phenotype relationships while comparative work in other insects has expanded our understanding of the evolution of insect eyes via gene duplication, coexpression and homologue switching. Even so, until recently, technology and sampling have limited our understanding of the fundamental mechanisms that evolution uses to shape the diversity of insect eyes. With the advent of genome editing and
in vitro
expression assays, the study of insect opsins is poised to reveal new frontiers in evolutionary biology, visual neuroscience, and animal behaviour.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Crustacean conundrums: a review of opsin diversity and evolution
Authors: Palecanda Sitara , Iwanicki Thomas , Steck Mireille , Porter Megan L.
Published: September 2022

Knowledge of crustacean vision is lacking compared to the more well-studied vertebrates and insects. While crustacean visual systems are typically conserved morphologically, the molecular components (i.e. opsins) remain understudied. This review aims to characterize opsin diversity across crustacean lineages for an integrated view of visual system evolution. Using publicly available data from 95 species, we identified opsin sequences and classified them by clade. Our analysis produced 485 putative visual opsins and 141 non-visual opsins. The visual opsins were separated into six clades: long wavelength sensitive (LWS), middle wavelength sensitive (MWS) 1 and 2, short wavelength or ultraviolet sensitive (SWS/UVS) and a clade of thecostracan opsins, with multiple LWS and MWS opsin copies observed. The SWS/UVS opsins were relatively conserved in most species. The crustacean classes Cephalocarida, Remipedia and Hexanauplia exhibited reduced visual opsin diversity compared to others, with the malacostracan decapods having the highest opsin diversity. Non-visual opsins were identified from all investigated classes except Cephalocarida. Additionally, a novel clade of non-visual crustacean-specific, R-type opsins (Rc) was discovered. This review aims to provide a framework for future research on crustacean vision, with an emphasis on the need for more work in spectral characterization and molecular analysis.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Colour vision in ants (Formicidae, Hymenoptera)
Authors: Yilmaz Ayse , Spaethe Johannes
Published: September 2022

Ants are ecologically one of the most important groups of insects and exhibit impressive capabilities for visual learning and orientation. Studies on numerous ant species demonstrate that ants can learn to discriminate between different colours irrespective of light intensity and modify their behaviour accordingly. However, the findings across species are variable and inconsistent, suggesting that our understanding of colour vision in ants and what roles ecological and phylogenetic factors play is at an early stage. This review provides a brief synopsis of the critical findings of the past century of research by compiling studies that address molecular, physiological and behavioural aspects of ant colour vision. With this, we aim to improve our understanding of colour vision and to gain deeper insights into the mysterious and colourful world of ants.

This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.
Systematic Engineering of Virus-Like Particles to Identify Self-Assembly Rules for Shifting Particle Size
Authors: Ikwuagwu Bon , Hartman Emily , Mills Carolyn , Tullman-Ercek Danielle
Published: September 2022

Virus-like particles (VLPs) are promising scaffolds for biomaterials as well as diagnostic and therapeutic applications. However, there are some key challenges to be solved, such as the ability to engineer alternate sizes for varied use cases. To this end, we created a library of MS2 VLP variants at two key residues in the coat protein which have been implicated as important to controlling VLP size and geometry. By adapting a method for systematic mutagenesis coupled with size-based selections and high-throughput sequencing as a readout, we developed a quantitative assessment of two residues in MS2 coat protein that govern the size shift in MS2 VLPs. We then applied the strategy to the equivalent residues in Qβ VLPs, an MS2 homolog, and demonstrate that the analogous pair of residues are also able to impact VLP size and shape. These results underscore the power of fitness landscapes in identifying critical features for assembly.
Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2
Authors: Frangos Zachary J. , Wilson Katie A. , Aitken Heather M. , Chater Ryan Cantwell , Vandenberg Robert J. , O’Mara Megan L.
Published: September 2022

Membrane cholesterol binds to and modulates the function of the specific SLC6 transporters. Here we investigate how cholesterol binds to and modulates the rate of glycine transport by the SLC6 glycine transporter GlyT2, and how this impacts lipid inhibition of GlyT2. Bioactive lipid inhibitors of GlyT2 are analgesics that bind to the lipid allosteric site of the outward facing GlyT2 conformation that is accessible from the extracellular solution. Using molecular dynamics simulations, mutagenesis and cholesterol depletion experiments, we show that bioactive lipid inhibition of glycine transport is modulated by the recruitment of membrane cholesterol to a cholesterol binding site formed by transmembrane helices 1, 5 and 7. Recruitment involves cholesterol flipping from its membrane orientation, and insertion of the 3’ hydroxyl group into the cholesterol binding cavity to interact with the base of the lipid allosteric site and the bound inhibitor. The recruitment of membrane cholesterol by allosteric GlyT2 inhibitors is a potential avenue for the development of high-potency, specific pain analgesics and could provide alternative therapeutics that target GlyT2 and other SLC6 neurotransmitter transporters.
Cortical Circuit Mechanisms of Multimodal Temporal Pattern Discrimination
Authors: Post Sam , Mol William , Abu-Wishah Omar , Ali Shazia , Rahmatullah Noorhan , Goel Anubhuti
Published: September 2022

Discriminating between temporal features in sensory stimuli is critical to complex behavior and decision making. However, how sensory cortical circuit mechanisms contribute to discrimination between subsecond temporal components in sensory events is unclear. To elucidate the mechanistic underpinnings of timing in primary visual cortex (V1), we recorded from V1 using 2-photon calcium imaging in awake-behaving mice performing a go/no-go discrimination timing task, which was composed of patterns of subsecond audio-visual stimuli. In both conditions, activity during the early stimulus period was temporally coordinated with the preferred stimulus. However, while network activity increased in the preferred condition, network activity was increasingly suppressed in the nonpreferred condition over the stimulus period. Our results demonstrate that discrimination between subsecond intervals that are contained in rhythmic patterns can be accomplished by local networks and suggest the contribution of neural resonance as a mechanism.
Endogenous tagging of Unc-13 reveals nanocluster reorganization at active zones during presynaptic homeostatic potentiation
Authors: Dannhäuser Sven , Mrestani Achmed , Gundelach Florian , Pauli Martin , Komma Fabian , Kollmannsberger Philip , Sauer Markus , Heckmann Manfred , Paul Mila M.
Published: September 2022

Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein mesh-work the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release.

We employ MiMIC-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system. Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13GFSTF 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13GFSTF, Bruchpilot and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13GFSTF nanoclusters that move towards the AZ center during PHP with unaltered Unc-13GFSTF protein levels.
ggcoverage: an R package to visualize and annotate genome coverage for various NGS data
Authors: Song Yabing , Wang Jianbin
Published: September 2022

Visualizing genome coverage is of vital importance to inspect and interpret various next-generation sequencing (NGS) data. However, existing tools that perform such visualizations remain inflexible, complicated, lack necessary annotations and the figures generated are not publication-quality. Here, we introduce ggcoverage, an R package with the grammar of graphics implemented in ggplot2, providing a flexible, programmable and user-friendly way to visualize genome coverage, multiple available annotations to adapt to different NGS data, and generating publication-quality plots.

Availability and Implementation

ggcoverage is an R package available via CRAN (https://cran.r-project.org/web/packages/ggcoverage/index.html) under MIT license. Support is available via GitHub (https://github.com/showteeth/ggcoverage/issues). Data used to generate figures are available on GitHub as example data.

Contact

songyb18@mails.tsinghua.edu.cn, jianbinwang@tsinghua.edu.cn.
A deep learning and digital archaeology approach for mosquito repellent discovery
Authors: Wei Jennifer N. , Ruiz Carlos , Vlot Marnix , Sanchez-Lengeling Benjamin , Lee Brian K. , Berning Luuk , Vos Martijn W. , Henderson Rob W.M. , Qian Wesley W. , Ando D. Michael , Groetsch Kurt M. , Gerkin Richard C. , Wiltschko Alexander B. , Riffel Jeffrey , Dechering Koen J.
Published: September 2022

Insect-borne diseases kill >0.5 million people annually. Currently available repellents for personal or household protection are limited in their efficacy, applicability, and safety profile. Here, we describe a machine-learning-driven high-throughput method for the discovery of novel repellent molecules. To achieve this, we digitized a large, historic dataset containing ∼19,000 mosquito repellency measurements. We then trained a graph neural network (GNN) to map molecular structure and repellency. We applied this model to select 317 candidate molecules to test in parallelizable behavioral assays, quantifying repellency in multiple pest species and in follow-up trials with human volunteers. The GNN approach outperformed a chemoinformatic model and produced a hit rate that increased with training data size, suggesting that both model innovation and novel data collection were integral to predictive accuracy. We identified >10 molecules with repellency similar to or greater than the most widely used repellents. We analyzed the neural responses from the mosquito antennal (olfactory) lobe to selected repellents and found a limited correlation between these responses and our GNN representation. This approach enables computational screening of billions of possible molecules to identify empirically tractable numbers of candidate repellents, leading to accelerated progress towards solving a global health challenge.
A Principal Odor Map Unifies Diverse Tasks in Human Olfactory Perception
Authors: Lee Brian K. , Mayhew Emily J. , Sanchez-Lengeling Benjamin , Wei Jennifer N. , Qian Wesley W. , Little Kelsie , Andres Matthew , Nguyen Britney B. , Moloy Theresa , Parker Jane K. , Gerkin Richard C. , Mainland Joel D. , Wiltschko Alexander B.
Published: September 2022

Mapping molecular structure to odor perception is a key challenge in olfaction. Here, we use graph neural networks (GNN) to generate a Principal Odor Map (POM) that preserves perceptual relationships and enables odor quality prediction for novel odorants. The model is as reliable as a human in describing odor quality: on a prospective validation set of 400 novel odorants, the model-generated odor profile more closely matched the trained panel mean (n=15) than did the median panelist. Applying simple, interpretable, theoretically-rooted transformations, the POM outperformed chemoinformatic models on several other odor prediction tasks, indicating that the POM successfully encoded a generalized map of structure-odor relationships. This approach broadly enables odor prediction and paves the way toward digitizing odors.

One-Sentence Summary

An odor map achieves human-level odor description performance and generalizes to diverse odor-prediction tasks.
Deep autoregressive generative models capture the intrinsics embedded in T-cell receptor repertoires
Authors: Jiang Yuepeng , Li Shuai Cheng
Published: September 2022

T-cell receptors (TCRs) play an essential role in the adaptive immune system. Probabilistic models for TCR repertoires can help decipher the underlying complex sequence patterns and provide novel insights into understanding the adaptive immune system. In this work, we develop TCRpeg, a deep autoregressive generative model to unravel the sequence patterns of TCR repertoires. TCRpeg outperforms state-of-the-art methods in estimating the probability distribution of a TCR repertoire, boosting the accuracy from 0.672 to 0.906 measured by the Pearson correlation coefficient. Furthermore, with promising performance in probability inference, TCRpeg improves on a range of TCR-related tasks: revealing TCR repertoire-level discrepancies, classifying antigen-specific TCRs, validating previously discovered TCR motifs, generating novel TCRs, and augmenting TCR data. Our results and analysis highlight the flexibility and capacity of TCRpeg to extract TCR sequence information, providing a novel approach to decipher complex immunogenomic repertoires.
Energy Crisis after Inter-System Mitochondria Transfer is the Direct Cause of Death by Sepsis
Authors: Tang Michael
Published: September 2022

Sepsis is one of the leading causes of death worldwide. With nearly 50 million incidences per year, it causes 11 million deaths worldwide annually, exceeding the 10 million total deaths caused by all tumors. Surprisingly, there is no specific drug available on market, explaining why it has a mortality rate as high as 22.5%. The lack of specific drug is mainly caused by the lack of understanding of how sepsis causes death. In this paper, I hypothesized that since energy production by mitochondria through respiration is not sustainable because the high level of reactive oxygen species (ROS) produced during respiration damages mitochondria themselves, mitochondria in the immune system cannot meet the dramatic and long-lasting high level of energy requirement of the system during sepsis. The immune system uses up all the functional mitochondria in the body by inter-system mitochondria transfer (ISMT), which dumps its used, unfunctional, or oxidized mitochondria to and recruits functional mitochondria from other systems. ISMT leads to the lack of functional mitochondria, hence energy, in the brain and the heart, and eventually causes death of the body. The hypothesis was supported by three key results: First, 2.5 hours after sepsis induction, mtDNA copy number increased dramatically in the spleen, brain, muscle, and blood, but decreased dramatically in the liver, kidneys, and skin. Second, mice died from sepsis showed a severe decline of mitochondria function in the brain and the heart. Finally, a single injection of isolated functional mitochondria to mice with sepsis reduced the mortality rate compared to mice received inactivated mitochondria.
Balancing true and false detection of intermittent sensory targets by adjusting the inputs to the evidence accumulation process
Authors: Geuzebroek Anna C. , Craddock Hannah , O’Connell Redmond G. , Kelly Simon P.
Published: September 2022

Decisions about noisy stimuli are widely understood to be made by accumulating evidence up to a decision bound that can be adjusted according to task demands. However, relatively little is known about how such mechanisms operate in continuous monitoring contexts requiring intermittent target detection. Here, we examined neural decision processes underlying detection of 1-second coherence-targets within continuous random dot motion, and how they are adjusted across contexts with Weak, Strong, or randomly Mixed weak/strong targets. Our prediction was that decision bounds would be set lower when weak targets are more prevalent. Behavioural hit and false alarm rate patterns were consistent with this, and were well-captured by a bound-adjustable leaky accumulator model. However, beta-band EEG signatures of motor preparation contradicted this, instead indicating lower bounds in the Strong-target context. We thus tested two alternative models in which decision bound dynamics were constrained directly by Beta measurements, respectively featuring leaky accumulation with adjustable leak, and non-leaky accumulation of evidence referenced to an adjustable sensory-level criterion. We found that the latter model best explained both behaviour and neural dynamics, highlighting novel means of decision policy regulation and the importance of neurally-informed modelling.
IL-10 inhibits STAT1-dependent macrophage accumulation during microbiota-induced colitis
Authors: Patik Izabel , Redhu Naresh S. , Eran Alal , Bao Bin , Nandy Anubhab , Tang Ying , El Sayed Shorouk , Shen Zeli , Glickman Jonathan , Fox James G. , Snapper Scott B. , Horwitz Bruce H.
Published: September 2022

Loss of IL-10R function leads to severe early onset colitis and in murine models is associated with the accumulation of immature inflammatory colonic macrophages. We have shown that IL-10R-deficient colonic macrophages exhibit increased STAT1-dependent gene expression, suggesting that IL-10R-mediated inhibition of STAT1 signaling in newly recruited colonic macrophages might interfere with the development of an inflammatory phenotype. Indeed Stat1-/- mice exhibit defects in colonic macrophage accumulation following Helicobacter hepaticus infection and IL-10R blockade, and this was phenocopied in mice lacking IFNGR, an inducer of STAT1 activation. Radiation chimeras demonstrated that reduced accumulation of STAT1-deficient macrophages was based on a cell-intrinsic defect. Unexpectedly, mixed radiation chimeras generated with both WT and IL-10R-deficient bone marrow indicated that rather than directly interfering with STAT1 function, IL-10R prevents the generation of a cell extrinsic signal that promotes the accumulation of immature macrophages. These results define essential mechanisms controlling inflammatory macrophage accumulation in inflammatory bowel diseases.

Intrinsic STAT1-function drives the accumulation of macrophages within the colon following the loss of IL-10R signaling. IL-10R prevents this STAT1-dependent process through a non-cell autonomous mechanism.
LRRK2-G2019S Synergizes with Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation that Precede Nigrostriatal Degeneration
Authors: Giachino Carmela , Tirolo Cataldo , Caniglia Salvatore , Serapide Maria F. , L’Episcopo Francesca , Bertoli Federico , Giuliano Claudio , Mearelli Marika , Jakobi Meike , Schneiderhan-Marra Nicole , Deleidi Michela , Marchetti Bianca
Published: September 2022

Background

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson’s disease (PD). The incomplete penetrance ofLRRK2mutations suggest that additional hits are required for disease onset. We hypothesized that chronic low-grade inflammation interacts with LRRK2 G2019S, the most frequent PD-associated mutation, to activate peripheral and central immune reactions and drive age-dependent neurodegeneration.

Methods and Results

We exposed wild-type and LRRK2 G2019S mice to a low chronic dose of lipopolysaccharide, and we performed a longitudinal analysis of central and peripheral immune reactions and neurodegeneration. Low-dose inflammation triggered nigrostriatal degeneration, macrophage/monocyte brain infiltration, and astro-/microgliosis. LRRK2 G2019S mice showed an early dysregulation of peripheral cytokines, increased CD4+T-cell infiltration and α-synuclein aggregation in the colon. Interestingly, peripheral immune activation and colonic α-synuclein aggregation precede astro-/microgliosis and neurodegeneration.

Conclusions

Our study suggests an early role of the peripheral immune system and the gut in LRRK2 PD and provides a novel model to study early therapeutic immune targets and biomarkers.
Imaging through Windansee electrode arrays reveals a small fraction of local neurons following surface MUA
Authors: Thunemann Martin , Hossain Lorraine , Ness Torbjørn V. , Rogers Nicholas , Lee Keundong , Lee Sang Heon , Kılıç Kıvılcım , Oh Hongseok , Economo Michael N. , Gilja Vikash , Einevoll Gaute T. , Dayeh Shadi A. , Devor Anna
Published: September 2022

Prior studies have shown that neuronal spikes can be recorded with microelectrode arrays placed on the cortical surface. However, the etiology of these spikes remains unclear. Because the top cortical layer (layer 1) contains very few neuronal cell bodies, it has been proposed that these spikes originate from neurons with cell bodies in layer 2. To address this question, we combined two-photon calcium imaging with electrophysiological recordings from the cortical surface in awake mice using chronically implanted PEDOT:PSS electrode arrays on transparent parylene C substrate.

Our electrode arrays (termed Windansee) were integrated with cortical windows offering see-through optical access while also providing measurements of local field potentials (LFP) and multiunit activity (MUA) from the cortical surface. To enable longitudinal data acquisition, we have developed a mechanical solution for installation, connectorization, and protection of Windansee devices aiming for an unhindered access for high numerical aperture microscope objectives and a lifetime of several months while worn by a mouse.

Contrary to the common notion, our measurements revealed that only a small fraction of layer 2 neurons from the sampled pool (~13%) faithfully followed MUA recorded from the surface above the imaging field-of-view. Surprised by this result, we turned to computational modeling for an alternative explanation of the MUA signal. Using realistic modeling of neurons with back-propagating dendritic properties, we computed the extracellular action potential at the cortical surface due to firing of local cortical neurons and compared the result to that due to axonal inputs to layer 1. Assuming the literature values for the cell/axon density and firing rates, our modeling results show that surface MUA due to axonal inputs is over an order of magnitude larger than that due to firing of layer 2 pyramidal neurons.

Thus, a combination of surface MUA recordings with two-photon calcium imaging can provide complementary information about the input to a cortical column and the local circuit response. Cortical layer I plays an important role in integration of a broad range of cortico-cortical, thalamocortical and neuromodulatory inputs. Therefore, detecting their activity as MUA while combining electrode recording with two-photon imaging using optically transparent surface electrode arrays would facilitate studies of the input/output relationship in cortical circuits, inform computational circuit models, and improve the accuracy of the next generation brain-machine interfaces.
Chemoenzymatic Measurement of Cell-surface Glycan in Single-cell Multiomics: LacNAc as an Example
Authors: Yu Wenhao , Zhao Xinlu , Jalloh Abubakar S. , Zhao Yingying , Dinner Brandon , Yang Yang , Ouyang Shian , Li Yachao , Tian Tian , Zhao Zihan , Yang Rong , Chen Mingkuan , Lauvau Gregoire , Guo Zijian , Wu Peng , Li Jie P.
Published: September 2022

Despite the rich information of a cell’s physiological state encoded in the dynamic changes of cell-surface glycans, methods of capturing glycosylation states at the single-cell level are quite limited. Here we report a chemoenzymatic single-cell N-acetyllactosamine (LacNAc) detection method via tagging the LacNAc with a specific DNA barcode. Compared to the lectin-based glycan detection, the chemoenzymatic labeling does not change the transcriptional status of immune cells and is more compatible with scRNA-seq. Integrated analysis of LacNAc and transcriptome of T cells at a single-cell level reveals that the quantity of cell-surface LacNAc is significantly upregulated in activated CD8+ T cells but maintained at the basal level in quiescent CD8+ T cells (i.e., naive and central memory T cells). Further analysis confirms that the LacNAc level is positively correlated to the glycolytic activity of CD8+ T cells at all statues. Taken together, our study demonstrates the feasibility of chemoenzymatic detection of cell-surface glycan in single-cell RNA sequencing-based multiomics with information of TCR sequence and cell-surface epitopes (i.e., scTCR and CITE-seq) and offers a new way to characterize the biological role of glycan in diversified physiological states.
Altered tau in rTg4510 mice after a single interfaced CHIMERA traumatic brain injury
Authors: Cheng Wai Hang , Cheung Honor , Kang Amy , Fan Jianjia , Cooper Jennifer , Anwer Mehwish , Barron Carlos , Wilkinson Anna , Hu Grace , Yue Jefferey , Cripton Peter A , Vocadlo David , Wellington Cheryl L
Published: September 2022

Traumatic brain injury (TBI) in an established risk factor for neurodegenerative disease. In this report, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to study the effects of a single moderate-severe TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice were impacted at 4.0J at 4-mo of age using interfaced CHIMERA and compared to sham controls. Immediately after injury, moderate-severe TBI induced significant mortality (7/15; 47%), and a prolonged duration of loss of righting reflex. At 2-mo post-injury, surviving mice displayed significant histological evidence of microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting showed that TBI mice had a reduced p-GSK-3β (S9):GSK-3β ratio, suggesting greater tau kinase activity. However, tauopathy in surviving TBI mice showed a divergent response, with 3/8 mice having a very low level of tau protein in brain lysates (i.e. lower than sham), and were thus analyzed separately from the other 5/8 TBI mice that maintained the expected level of total tau. Compared to sham controls, TBI mice with normal tau levels had increased p-tau (PHF1 and AT8), increased autophagolysosome accumulation (p62 and Cathepsin D) and decreased hippocampal size. These findings were not observed in TBI mice with low total tau levels. These observations suggest that TBI leads to chronic white matter injury and altered GSK-3β activity. However, post-injury tauopathy and autophagolysosome accumulation diverged in surviving mice through mechanisms that remain to be defined.
Sensory uncertainty punctuates motor learning independently of movement error when both feedforward and feedback control processes are engaged
Authors: Hewitson Christopher L. , Kaplan David M. , Crossley Matthew J.
Published: September 2022

Integrating sensory information during movement and adapting motor plans over successive movements are both essential for accurate, flexible motor behavior. When an ongoing movement is off target, feedback control mechanisms update the descending motor commands to counter the sensed error. Over longer timescales, errors induce adaptation in feedforward planning so that future movements become more accurate and require less online adjustment from feedback control processes. Both the degree to which sensory feedback is integrated into an ongoing movement and the degree to which movement errors drive adaptive changes in feedforward motor plans have been shown to scale inversely with sensory uncertainty. However, since they have only been studied in isolation of each other, little is know about how they respond to sensory uncertainty in real-world movement contexts where they co-occur. Here, we show that sensory uncertainty impacts feedforward adaptation of reaching movements differently when feedback integration is present versus when it is absent. In particular, participants gradually adjust their movements from trial-to-trial in a manner that is well characterised by a slow and consistent envelope of error reduction. Riding on top of this slow envelope, participants display large and abrupt changes in their initial movement vectors that clearly correlate with the degree of sensory uncertainty present on the previous trial. However, these abrupt changes are insensitive to the magnitude and direction of the sensed movement error. These results prompt important questions for current models of sensorimotor learning under uncertainty and open up exciting new avenues for future exploration.

Author Summary

A large body of literature shows that sensory uncertainty inversely scales the degree of error-driven corrections made to motor plans from one trial to the next. However, by limiting sensory feedback to the endpoint of movements, these studies prevent corrections from taking place during the movement. Here, we show that when such corrections are promoted, sensory uncertainty punctuates between-trial movement corrections with abrupt changes that closely track the degree of sensory uncertainty but are insensitive to the magnitude and direction of movement error. This result marks a significant departure from existing findings and opens up new paths for future exploration.