Miracle-dz/UniFAR-FTUs huggingface dataset:
CD23+IgG1+ memory B cells are poised to switch to pathogenic IgE production in food allergy

Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23+IgG1+ memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23+IgG1+ memory B cells correlated with circulating concentrations of IgE in children with peanut allergy. A corresponding population of “type 2–marked” IgG1+ memory B cells was identified in single-cell RNA sequencing experiments. These cells differentially expressed interleukin-4 (IL-4)– and IL-13–regulated genes, such as FCER2/CD23+, IL4R, and germline IGHE, and carried highly mutated B cell receptors (BCRs). In children with high concentrations of serum peanut-specific IgE, high-affinity B cells that bind the main peanut allergen Ara h 2 mapped to the population of “type 2–marked” IgG1+ memory B cells and included clones with convergent BCRs across different individuals. Our findings indicate that CD23+IgG1+ memory B cells transcribing germline IGHE are a unique memory population containing precursors of high-affinity pathogenic IgE-producing cells that are likely to be involved in the long-term persistence of peanut allergy. A population of IgG+ memory B cells in peanut-allergic individuals contains high-affinity allergen-specific clones and is poised to switch to IgE. Editor’s summary IgE is the key mediator of allergic responses in the context of both food allergy and allergic rhinitis. However, most IgE-producing cells are short-lived, begging the question: What population replenishes the IgE-producing cell pool? In a pair of papers, Ota et al. and Koenig et al. independently identified a population of type 2–polarized memory B cells expressing IgG1 or IgG4, CD23, and IL-4Rα that also express germline IGHE. Ota et al. found that these cells were enriched in children with peanut allergy as compared with non-allergic pediatric controls, expressed highly mutated B cell receptors specific to peanuts, and had a high ability to switch to IgE in vitro. Koenig et al. identified a comparable cell type in adults with birch allergy, house dust mite allergy, or peanut allergy and found that these memory B cells generated allergen-specific IgE during early sublingual allergen immunotherapy. Together, these studies implicate type 2–polarized memory B cells expressing IgG, CD23, and IL-4Rα as the source of pathogenic, allergen-specific IgE-producing cells. —Courtney Malo
Fluctuating salinity during development impacts fish productivity

Climate change is elevating salinity levels in many freshwater systems, and more erratic rainfall is increasing variation in salinity. Consequently, many species now experience more extreme developmental environments. Resultant shifts in developmental trajectories could change key life history traits that persist into adulthood. To date, however, how variation in salinity affects the life histories of freshwater species has been neglected despite its implications for fisheries. We ran a large-scale experiment with a global pest, the mosquitofish (Gambusia holbrooki), and manipulated the salinity experienced by juveniles: freshwater (0‰), stable salinity (10‰) or fluctuating salinity (0-20‰; mean = 10 ‰). Fish developing in stable, high salinity grew faster and matured earlier, albeit with a decline in male telomeres and female gut development. Stable high salinity resulted in larger adult body size in females, but not males, which increased female fecundity. Conversely, fluctuations in salinity induced fish to grow more slowly and lowered female fecundity. Crucially, several of the long-term effects of salinity fluctuations were sex-specific, more adversely affecting females than males. We highlight that environmental variability alters an organism’s vulnerability to stressors, with implications that should be considered if we wish to understand the impact of climate change on population dynamics.
Limb, not touch location, is coded in 3D space

Skin location of touch is said to be recoded, by default, into a 3D-spatial location. Here, human participants received tactile stimulus pairs on a common or on two different limbs and judged either whether stimuli had occurred on the same limb, or on a common side of space. Misaligning skin and 3D-spatial codes through limb crossing had a stronger effect on spatial than on limb judgments, contradicting the notion that the 3D location of touch is readily available. Additionally, crossing effects were significantly reduced when stimulus pairs lay in a common dermatome, suggesting that limb choice was based on anatomical, not 3D-spatial, stimulus information. These results suggest that it is limbs, not touch, which are coded in 3D space. Commonly observed errors in reporting where touch occurred on the body depend on confusion due to where the touched limb usually resides with the spatial layout of the currently action-relevant limbs.
Spatial transcriptomics reveals distinct lineage identities for major and minor vein initiation during maize leaf development

Leaves of flowering plants are characterised by diverse venation patterns. Patterning begins with the selection of vein-forming procambial initial cells from within the ground meristem of a developing leaf, a process which is considered to be auxin-dependent, and continues until veins are anatomically differentiated with functional xylem and phloem. At present, the mechanisms responsible for leaf venation patterning are primarily characterized in the model eudicot Arabidopsis thaliana which displays a reticulate venation network. However, evidence suggests that vein development may proceed via a different mechanism in monocot leaves where venation patterning is parallel. Here, we employed spatial transcriptomics to analyse the spatiotemporal localisation of a subset of auxin related genes and candidate regulators of vein patterning in maize leaves. We show how different combinations of auxin influx and efflux transporters are recruited during leaf and vein specification, and how major and minor vein ranks develop with distinct identities. The localisation of the procambial marker PIN1a and the spatial arrangement of procambial initial cells that give rise to major and minor vein ranks further suggests that vein spacing is pre-patterned across the medio-lateral leaf axis prior to accumulation of the PIN1a auxin transporter. In contrast, patterning in the adaxial-abaxial axis occurs progressively, with markers of xylem and phloem gradually becoming polarised as differentiation proceeds. Collectively our data suggest that both lineage- and position-based mechanisms underpin vein patterning in maize leaves. SIGNIFICANCE STATEMENT During the development of multicellular organisms specialized cell-types differentiate from pluripotent stem cells, with cell identity acquired via lineage- or position-based mechanisms. In plants, most organs develop post-embryogenesis and as such developmental processes are influenced by the external environment. To adapt to different environmental contexts and yet still form recognizable organs, tissues and cell-types, position-based differentiation mechanisms are deployed in which cells adopt a certain fate depending on the activity of neighbouring cells. Such is the prevalence of position-based mechanisms in plant development that a role for lineage is rarely contemplated. Here we provide a rare example of lineage-based specification in maize where stem cells that give rise to different leaf vein types are inherently distinct at inception.
The role of ultradian rhythms in post-deprivation rebounds and diurnal rhythms of sleep and wakefulness in rats

The temporal organization of ultradian rhythms in sleep and wakefulness during post-sleep deprivation (TSD) rebound were investigated in 15 rats under contant bright light (LL). Following baseline recordings, rats were subjected to TSD using gentle manual stimulation. Post-TSD rebounds in cumulative wakefulness (WAKE), rapid eye movement sleep (REM) and non-REM sleep (NREM) were analyzed in WAKE-dominant (υw) and sleep-dominant (υs) ultradian phases. Rebounds in WAKE and NREM were present only when data were analyzed on a full ultradian cycle basis, and were absent in υs and υw phases alone. These rebounds were approximately 50% complete and not proportional to TSD excess/deficit. Rebounds in REM were present in full ultradian cycles and partially expressed in υs but absent in υw. REM rebounds fully compensated for REM deficit. Rebounds were mediated mainly by a reduction in the duration of the υw ultradian phase, and by decreased probability of arousal in the υs ultradian phase. These mechanisms were also found to partially mediate diurnal rhythms in 10 rats under a 12:12 h LD cycle. This study implicates an ultradian timing mechanism in the control of post-TSD rebounds and suggests that rebounds in all three states are mainly mediated by post-TSD adjustments in WAKE-promoting mechanisms. Ultradian rhythms should be taken into account to avoid errors in data analysis. Highlights Sleep-wake state exhibits circadian rhythms and ultradian rhythms. These rhythms interact with rebounds after sleep deprivation. Circadian amplitude and sleep rebound are partially mediated by ultradian timing. Arousal-related processes control these sleep-wake patterns in both states. Measuring ultradian rhythms is necessary for accurate analysis of data.
Sex Differences in the Brain’s White Matter Microstructure during Development assessed using Advanced Diffusion MRI Models

Typical sex differences in white matter (WM) microstructure during development are incompletely understood. Here we evaluated sex differences in WM microstructure during typical brain development using a sample of neurotypical individuals across a wide developmental age (N=239, aged 5-22 years). We used the conventional diffusion-weighted MRI (dMRI) model, diffusion tensor imaging (DTI), and two advanced dMRI models, the tensor distribution function (TDF) and neurite orientation dispersion density imaging (NODDI) to assess WM microstructure. WM microstructure exhibited significant, regionally consistent sex differences across the brain during typical development. Additionally, the TDF model was most sensitive in detecting sex differences. These findings highlight the importance of considering sex in neurodevelopmental research and underscore the value of the advanced TDF model.
Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed a novel approach-avoidance conflict model using a modified conditioned place preference paradigm to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision making. Upon establishment of morphine conditioned place preference, rats underwent a subsequent conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline control group avoided the cat odor side, the morphine group maintained preference for the paired side despite the presence of cat odor. K-means clustering identified two subsets of morphine-treated rats that exhibited either persistent drug seeking (Risk-Takers) or increased avoidance (Risk-Avoiders) during conflict. Single-unit recordings from the prelimbic cortex (PL) revealed decreased neuronal firing rates upon acute morphine exposure in both Risk-Takers and Risk-Avoiders, but this firing rate suppression was absent after repeated administration. Risk-Avoiders also displayed distinct post-morphine excitation in PL which persisted across conditioning. During the preference test, subpopulations of PL neurons in all groups were either excited or inhibited when rats entered the paired side. Interestingly, while this inhibitory signal was lost during the subsequent conflict test in both saline and Risk-Avoider groups, these inhibitory responses persisted in Risk-Takers. Our results suggest that loss of PL inhibition after opioid conditioning is associated with the formation of contextual reward memory. Furthermore, persistent PL inhibitory signaling in the drug-associated context during conflict may underlie increased risk taking following opioid exposure.
Improving rice drought tolerance through host-mediated microbiome selection

Plant microbiome engineering remains a significant challenge due to challenges associated with accurately predicting microbiome assembly and function in complex, heterogeneous soil environments. However, host-mediated selection can simplify the process by using plant host phenotype as a reporter of microbiome function; by iteratively selecting microbiomes from hosts with desired phenotypes and using them to inoculate subsequent cohorts of hosts, artificial selection can steer the microbiome towards a composition producing optimized plant phenotypes. In this study, we inoculated rice with wild microbial communities from fallow rice field, desert, and serpentine seep field soils. By challenging these plants with drought and iteratively selecting microbiomes from the least drought stressed plants across multiple generations, we derived simplified microbiomes that enhanced both the growth and drought tolerance of rice. Across selection cycles, microbiomes within and between soil treatments became increasingly similar, implicating both dispersal and selection as drivers of community composition. With amplicon sequencing data we identified specific bacterial taxa associated with improved rice drought phenotypes; while many of these taxa have been previously described as plant growth promoters, we also identified novel taxa exhibiting strong positive correlation with improved drought performance. Lastly, we resolved 272 metagenome-assembled genomes (MAGs) and used these MAGs to identify functions enriched in bacteria driving enhanced drought tolerance. The most significantly enriched functions—particularly glycerol-3-phosphate and iron transport—have been previously implicated as potential mediators of plant-microbe interactions during drought. Altogether, these data demonstrate that host-mediated selection provides an efficient framework for microbiome engineering through the identification of both individual taxa and simplified communities associated with enhanced plant phenotypes.
High-throughput identification of the spatial origins of Drosophila optic lobe neurons using single-cell mRNA-sequencing

The medulla is the largest neuropil of the Drosophila optic lobe. It contains about 100 neuronal types that have been comprehensively characterized morphologically and molecularly. These neuronal types are specified from a larval neuroepithelium called the Outer Proliferation Center (OPC) via the integration of temporal, spatial, and Notch-driven mechanisms. Although we recently characterized the temporal windows of origin of all medulla neurons, as well as their Notch status, their spatial origins remained unknown. Here, we isolated cells from different OPC spatial domains and performed single-cell mRNA-sequencing to identify the neuronal types produced in these domains. This allowed us to characterize in a high-throughput manner the spatial origins of all medulla neurons and to identify two new spatial subdivisions of the OPC. Moreover, our work shows that the most abundant neuronal types are produced from epithelial domains of different sizes despite being present in a similar number of copies. Combined with our previously published scRNA-seq developmental atlas of the optic lobe, our work opens the door for further studies on how specification factor expression in progenitors impacts gene expression in developing and adult neurons.
Deep learning-based location decoding reveals that across-day representational drift is better predicted by rewarded experience than time

Neural representations of space in the hippocampus and related brain areas change over timescales of days-weeks, even in familiar contexts and when behavior appears stable. It is unclear whether this ‘representational drift’ is primarily driven by the passage of time or by behavioral experience. Here we present a novel deep-learning approach for measuring network-level representational drift, quantifying drift as the rate of change in decoder error of deep neural networks as a function of train-test lag. Using this method, we analyse a longitudinal dataset of 0.5–475 Hz broadband local field potential (LFP) data recorded from dorsal hippocampal CA1, medial prefrontal cortex and parietal cortex of six rats over ∼30 days, during learning of a spatial navigation task in an unfamiliar environment. All three brain regions contained clear spatial representations which improve and drift over training sessions. We find that the rate of drift slows for later training sessions. Finally, we find that drift is statistically better explained by task-relevant rewarded experiences within the maze, rather than the passage of time or number of sessions the animal spent on the maze. Our use of deep neural networks to quantify drift in broadband neural time series unlocks new possibilities for testing which aspects of behavior drive representational drift.
Expression of novel androgen receptors in three GnRH neuron subtypes in the cichlid brain

Within a social hierarchy, an individuals’ social status determines its physiology and behavior. In A. burtoni, subordinate males can rise in rank to become dominant, which is accompanied by the upregulation of the entire HPG axis, including activation of GnRH1 neurons, a rise in circulating androgen levels and the display of specific aggressive and reproductive behaviors. Cichlids possess two other GnRH subtypes, GnRH2 and GnRH3, the latter being implicated in the display of male specific behaviors. Interestingly, some studies showed that these GnRH neurons are responsive to fluctuations in circulating androgen levels, suggesting a link between GnRH neurons and androgen receptors (ARs). Due to a teleost-specific whole genome duplication, A. burtoni possess two AR paralogs (ARα and ARβ) that are encoded by two different genes, ar1 and ar2, respectively. Even though social status has been strongly linked to androgens, whether ARα and/or ARβ are present in GnRH neurons remains unclear. Here, we used immunohistochemistry and in situ hybridization chain reaction (HCR) to investigate ar1 and ar2 expression specifically in GnRH neurons. We find that all GnRH1 neurons intensely express ar1 but only a few of them express ar2, suggesting the presence of genetically-distinct GnRH1 subtypes. Very few ar1 and ar2 transcripts were found in GnRH2 neurons. GnRH3 neurons were found to express both ar genes. The presence of distinct ar genes within GnRH neuron subtypes, most clearly observed for GnRH1 neurons, suggests differential control of these neurons by androgenic signaling. These findings provide valuable insight for future studies aimed at disentangling the androgenic control of GnRH neuron plasticity and reproductive plasticity across teleosts.
Nanopore-based DNA long-read sequencing analysis of the aged human brain

Aging disrupts cellular processes such as DNA repair and epigenetic control, leading to a gradual buildup of genomic alterations that can have detrimental effects in post-mitotic cells. Genomic alterations in regions of the genome that are rich in repetitive sequences, often termed “dark loci,” are difficult to resolve using traditional sequencing approaches. New long-read technologies offer promising avenues for exploration of previously inaccessible regions of the genome. Using nanopore-based long-read whole-genome sequencing of DNA extracted from aged 18 human brains, we identify previously unreported structural variants and methylation patterns within repetitive DNA, focusing on transposable elements (“jumping genes”) as crucial sources of variation, particularly in dark loci. Our analyses reveal potential somatic insertion variants and provides DNA methylation frequencies for many retrotransposon families. We further demonstrate the utility of this technology for the study of these challenging genomic regions in brains affected by Alzheimer’s disease and identify significant differences in DNA methylation in pathologically normal brains versus those affected by Alzheimer’s disease. Highlighting the power of this approach, we discover specific polymorphic retrotransposons with altered DNA methylation patterns. These retrotransposon loci have the potential to contribute to pathology, warranting further investigation in Alzheimer’s disease research. Taken together, our study provides the first long-read DNA sequencing-based analysis of retrotransposon sequences, structural variants, and DNA methylation in the aging brain affected with Alzheimer’s disease neuropathology.
Elevated Activity in Left Homologous Music Circuits is Maladaptive for Music Perception but Mediated by Decoupled Structure and Function

Music is inherent in human life and is a significant topic of cognitive neuroscience. Previous studies focused on amusia suggested that two frontotemporal circuits engage in music processing. Structure-function coupling is an important feature of human brain, which is associated with cognition and allows for a more sensitive investigation of brain-behavior association. However, we still have limited knowledge about the relation between structure-function coupling, music processing and other regional neural profiles. We recruited 106 participants (43 subjects were diagnosed with congenital amusia) and measured their music perception by Montreal Battery of Evaluation of Amusia (MBEA). Then we utilized support vector regression algorithm and mediation analysis, and employed amplitude of low frequency fluctuation (ALFF), structural/functional degree centrality (DC) and structure-function coupling to explore their relation with global averaged MBEA score. We found structure-function coupling of widespread brain regions in both hemispheres, rather than ALFF or DC, contributed to predict MBEA score. Left middle frontal gyrus, bilateral inferior temporal gyrus and right insula were most predictive regions, and these regions were involved in memory and cognitive control according to meta-analysis. Further, coupling of left middle frontal gyrus, a region that is homologous to and is connected with typical music circuits, fully mediated the negative relation between ALFF and MBEA score. Our findings provide further understanding for the neural basis of music, and have implications for neural plasticity, neuromodulation therapy and cognitive causes of amusia. Highlights Our study first applies structure-function coupling to investigate the neural correlates of music perception, and predicting modeling indicate structure-function coupling is more effective than regional activity and connectivity. Elevated activity of contralateral homologous of music circuits might be maladaptive rather than compensatory. Elevated spontaneous regional activity disrupts their connections, which might be a specific expression of neural plasticity for certain regions. Our findings have implications for cognitive causes (abnormal memory and/or cognitive control to music salients) of amusia.
Active Learning of Deterministic Transducers with Outputs in Arbitrary Monoids

We study monoidal transducers, transition systems arising as deterministic automata whose transitions also produce outputs in an arbitrary monoid, for instance allowing outputs to commute or to cancel out. We use the categorical framework for minimization and learning of Colcombet, Petrişan and Stabile to recover the notion of minimal transducer recognizing a language, and give necessary and sufficient conditions on the output monoid for this minimal transducer to exist and be unique (up to isomorphism). The categorical framework then provides an abstract algorithm for learning it using membership and equivalence queries, and we discuss practical aspects of this algorithm’s implementation