Miracle-dz/UniFAR-FTUs huggingface dataset:
Attention improves information flow between neuronal populations without changing the communication subspace

Visual attention allows observers to flexibly use or ignore visual information, suggesting that information can be flexibly routed between visual cortex and neurons involved in decision-making. We investigated the neural substrate of flexible information routing by analyzing the activity of populations of visual neurons in the medial temporal area (MT) and oculomotor neurons in the superior colliculus (SC) while rhesus monkeys switched spatial attention. We demonstrated that attention increases the efficacy of visuomotor communication: trial-to-trial variability of the population of SC neurons was better predicted by the activity of MT neurons (and vice versa) when attention was directed toward their joint receptive fields. Surprisingly, this improvement in prediction was not explained or accompanied by changes in the dimensionality of the shared subspace or in local or shared pairwise noise correlations. These results suggest a mechanism by which visual attention can affect perceptual decision-making without altering local neuronal representations.
Joint representation of working memory and uncertainty in human cortex

Neural representations of visual working memory (VWM) are noisy, and thus, decisions based on VWM are inevitably subject to uncertainty. However, the mechanisms by which the brain simultaneously represents the content and uncertainty of memory remain largely unknown. Here, inspired by the theory of probabilistic population codes, we test the hypothesis that the human brain represents an item maintained in VWM as a probability distribution over stimulus feature space, thereby capturing both its content and uncertainty. We used a neural generative model to decode probability distributions over memorized locations from fMRI activation patterns. We found that the mean of the probability distribution decoded from retinotopic cortical areas predicted memory reports on a trial-by-trial basis. Moreover, in several of the same mid-dorsal stream areas the spread of the distribution predicted subjective trial-by-trial uncertainty judgments. These results provide evidence that VWM content and uncertainty are jointly represented by probabilistic neural codes.
Disentangling the roles of inter- and intraspecific variation on leaf trait distributions across the eastern United States

Functional traits are influenced by phylogenetic constraints and environmental conditions, but previous large-scale studies modeled traits either as species weighted averages or directly from the environment, precluding analyses of the relative contributions of inter- and intraspecific variation across regions. We developed a joint model integrating phylogenetic and environmental information to understand and predict the distribution of eight leaf traits across the eastern USA. This model explained 68% of trait variation, outperforming both species-only and environment-only models, with variance attributable to species alone (23%), the environment alone (13%), and their combined effects (25%). The importance of the two drivers varied by trait. Predictions for the eastern USA produced accurate estimates of intraspecific variation and deviated from both species-only and environment-only models. Predictions revealed that intraspecific variation holds information across scales, affects relationships in the leaf economic spectrum and is key for interpreting trait distributions and ecosystem processes within and across ecoregions.
Memory Specific to Temporal Features of Sound Is Formed by Cue-Selective Enhancements in Temporal Coding Enabled by Inhibition of an Epigenetic Regulator

Recent investigation of memory-related functions in the auditory system have capitalized on the use of memory-modulating molecules to probe the relationship between memory and substrates of memory in auditory system coding. For example, epigenetic mechanisms, which regulate gene expression necessary for memory consolidation, are powerful modulators of learning-induced neuroplasticity and long-term memory (LTM) formation. Inhibition of the epigenetic regulator histone deacetylase 3 (HDAC3) promotes LTM, which is highly specific for spectral features of sound. The present work demonstrates for the first time that HDAC3 inhibition also enables memory for temporal features of sound. Adult male rats trained in an amplitude modulation (AM) rate discrimination task and treated with a selective inhibitor of HDAC3 formed memory that was highly specific to the AM rate paired with reward. Sound-specific memory revealed behaviorally was associated with a signal-specific enhancement in temporal coding in the auditory system; stronger phase locking that was specific to the rewarded AM rate was revealed in both the surface-recorded frequency following response and auditory cortical multiunit activity in rats treated with the HDAC3 inhibitor. Furthermore, HDAC3 inhibition increased trial-to-trial cortical response consistency (relative to naive and trained vehicle-treated rats), which generalized across different AM rates. Stronger signal-specific phase locking correlated with individual behavioral differences in memory specificity for the AM signal. These findings support that epigenetic mechanisms regulate activity-dependent processes that enhance discriminability of sensory cues encoded into LTM in both spectral and temporal domains, which may be important for remembering spectrotemporal features of sounds, for example, as in human voices and speech. SIGNIFICANCE STATEMENT Epigenetic mechanisms have recently been implicated in memory and information processing. Here, we use a pharmacological inhibitor of HDAC3 in a sensory model of learning to reveal the ability of HDAC3 to enable precise memory for amplitude-modulated sound cues. In so doing, we uncover neural substrates for memory's specificity for temporal sound cues. Memory specificity was supported by auditory cortical changes in temporal coding, including greater response consistency and stronger phase locking. HDAC3 appears to regulate effects across domains that determine specific cue saliency for behavior. Thus, epigenetic players may gate how sensory information is stored in long-term memory and can be leveraged to reveal the neural substrates of sensory details stored in memory.
MiR-137 and miR-122, two outer subventricular zone-enriched non-coding RNAs, regulate basal progenitor expansion and neuronal differentiation

Cortical expansion in the primate brain relies on the presence and the spatial enlargement of multiple germinal zones during development and on a prolonged developmental period. In contrast to other mammals, which have two cortical germinal zones, the ventricular zone (VZ) and subventricular zone (SVZ), gyrencephalic species display an additional germinal zone, the outer subventricular zone (OSVZ), which role is to increase the number and types of neurons generated during corticogenesis. How the OSVZ emerged during evolution is poorly understood but recent studies suggest a role for non-coding RNAs, which allow tight regulations of transcriptional programs in time and space during development (Dehay et al. 2015; Arcila et al., 2014). Here, using in vivo functional genetics, single-cell RNA sequencing, live imaging and electrophysiology to assess progenitor and neuronal properties in mice, we identify two ferret and human OSVZ-enriched microRNAs (miR), miR-137 and miR-122, which regulate key cellular features associated with cortical expansion. MiR-137 promotes basal progenitor self-replication and superficial layer neuron fate, while miR-122 slows down neuronal differentiation pace. Together, these findings support a cell-type specific role for miR-mediated transcriptional regulation in cortical expansion.
Eco-evolutionary dynamics lead to functionally robust and redundant communities

Microbial communities are functionally stable and taxonomically variable: species abundances fluctuate over time and space, while the functional composition is robust and reproducible. These observations imply functional redundancy: the same function is performed by many species, so that one may assemble communities with different species but the same functional composition. The clarity of this observation does not parallel with a theoretical understanding of its origin. Here we study the eco-evolutionary dynamics of communities interacting through competition and cross-feeding. We show that the eco-evolutionary trajectories rapidly converge to a “functional attractor”, characterized by a functional composition uniquely determined by environmental conditions. The taxonomic composition instead follows non-reproducible dynamics, constrained by the conservation of the functional composition. Our framework provides a deep theoretical foundation to the empirical observations of functional robustness and redundancy.
Contact-tracing in cultural evolution: a Bayesian mixture model to detect geographic areas of language contact

When speakers of two or more languages interact, they are likely to influence each other: contact leaves traces in the linguistic record, which in turn can reveal geographic areas of past human interaction and migration. However the complex, multi-dimensional nature of contact has hindered the development of a rigorous methodology for detecting its traces. Specifically, other factors may contribute to similarities between languages. Inheritance (a property is passed from an ancestor to several descendant languages), and universal preference (a property is universally preferred), may both overshadow contact signals. How can we find geographic contact areas in language data, while accounting for the confounding effects of inheritance and universal preference? We present sBayes, an algorithm for Bayesian clustering in the presence of confounding effects. The algorithm learns which similarities in a set of features are better accounted for by confounders, and which are due to contact effects. Contact areas are free to take any shape or size, but an explicit geographic prior ensures their spatial coherence. We test the clustering method on simulated data and apply it in two case studies to reveal language contact in South America and the Balkans. Our results are supported by —mostly qualitative— findings from previous studies. While we focus on the specific problem of language contact, the method can also be used to uncover other traces of shared history in cultural evolution, and more generally, to reveal latent spatial clusters in the presence of confounders.
A hierarchical process model links behavioral aging and lifespan in C. elegans

Individuals who remain vigorous longer tend to live longer, supporting the design of predictive behavioral biomarkers of aging. In C. elegans, the timing of age-associated vigorous movement cessation (VMC) and lifespan correlate strongly between individuals. However, many genetic and pharmaceutical interventions that alter aging produce disproportional effects on VMC and lifespan, appearing to “uncouple” the rate of behavioral aging and lifespan. To study the causal structure underlying such uncoupling, we developed a high-throughput, automated imaging platform to quantify behavioral aging and lifespan at an unprecedented scale. Our method reveals an inverse correlation between each individuals’ vigorous movement span and their remaining lifespan. Robust across many lifespan-altering interventions including a new RNA-polymerase II auxin-inducible degron system, our data shows that individual C. elegans experience at least two distinct but coupled physical declines—one governing VMC and the other governing lifespan. Through simulations and modeling, we clarify the causal relationship between these two “biological ages” and highlight a crucial but often untested assumption in conventional aging biomarker research: predictive biomarkers may not always report on the same biological age as that which determines long-term health outcomes.
Evolution of the Insect PPK Gene Family

Insect Pickpocket (PPK) receptors mediate the detection of stimuli of diverse sensory modalities, therefore having a relevant role for environmental sounding. Notwithstanding their relevance, studies on their evolution are scarce. We have analyzed the genomes of 26 species belonging to 8 insect orders (Blattodea, Orthoptera, Hemiptera, Phthiraptera, Hymenoptera, Lepidoptera, Coleoptera, and Diptera) to identify their PPK repertoires and study the evolution of this gene family. PPKs were detected in all genomes analyzed, with a total of 578 genes identified that distributed in 7 subfamilies. Our phylogenetic analysis allowed clarifying that the ppk17 gene appears to be the most divergent family member, composing a new group designed as subfamily VII. According to our analysis, PPKs evolved under a birth-and-death model that generated lineage-specific expansions usually located in clusters and the effect of strong purifying selection was seen for several orthogroups. Subfamily V was the largest one, presenting half of all PPKs studied, including a mosquito-specific expansion that can be considered a new target for pest control. Consistently with their sensory role, PPKs present a high gene turnover that generated considerable variation in the size of insect repertoires: Musca domestica (59), Blattella germanica (41), Culex quinquefasciatus (48), and Aedes albopictus (51) presented the largest PPK repertoires, while Pediculus humanus (only ppk17), bees and ants (6-9) had the smallest ones. The expansions identified in M. domestica and Bl. germanica also show promise as specific targets for controlling these nuisance insects. Our phylogenetic analysis revealed a subset of prevalent PPKs across insect genomes, suggesting a very conserved function that resembles the case of antennal ionotropic receptors. Finally, we identified new highly conserved residues in the second transmembrane domain that may be key for receptor function. Besides, more than a hundred PPK sequences presented calmodulin binding motifs, suggesting that at least some members of this family may amplify sensory responses as previously proposed for D. melanogaster ppk25. Overall, our study is a first attempt to characterize the evolutionary history of this family of sensory receptors, revealing relevant unknown features and clade-specific expansions.
Localizing Brain Function Based on Full Multivariate Activity Patterns: The Case of Visual Perception and Emotion Decoding

Multivariate statistics and machine learning methods have become a common tool to extract information represented in the brain. What is less recognized is that, in the process, it has become more difficult to perform data-driven discovery and functional localization. This is because multivariate pattern analysis (MVPA) studies tend to restrict themselves to a subset of the available data, or because sound inference to map model parameters back to brain anatomy is lacking. Here, we present a high-dimensional (including brain-wide) multivariate classification pipeline for the detection and localization of brain functions during tasks. In particular, we probe it at visual and socio-affective states in a task-oriented functional magnetic resonance imaging (fMRI) experiment. Classification models for a group of human participants and existing rigorous cluster inference methods are used to construct group anatomical-statistical parametric maps, which correspond to the most likely neural correlates of each psychological state. This led to the discovery of a multidimensional pattern of macroscale brain activity which reliably encodes for the perception of happiness in the visual cortex, lingual gyri and the posterior perivermian cerebellum. We failed to find similar evidence for sadness and anger. Anatomical consistency of discriminating features across subjects and contrasts despite the high number of dimensions suggests MVPA is a viable tool for a complete functional mapping pipeline, and not just the prediction of psychological states.
Susceptibility of rosaceous fruits and apple cultivars to postharvest rot by Paecilomyces niveus

Paecilomyces rot of apples is a postharvest disease caused by Paecilomyces niveus, a problematic spoiling agent of fruit juices and derivatives. The fungus produces ascospores that can survive food processing and germinate in finished fruit products. Processing apple fruits infected with Paecilomyces rot can lead to P. niveus contaminated juices. Because the fungus produces the mycotoxin patulin, juice spoilage by P. niveus is an important health hazard. Little is known about the disease biology and control mechanisms of this recently described postharvest disease. Following Koch’s postulates, we determined that a range of previously untested rosaceous fruits and popular apple cultivars are susceptible to Paecilomyces rot infection. We also observed that two closely related food spoiling fungi, Paecilomyces fulvus and Paecilomyces variotti, were unable to infect, cause symptoms in, or reproduce in wounded fruits. Our results highlight the unique abilities of Paecilomyces niveus to infect a variety of fruits, produce patulin, and form highly-resistant spores capable of spoiling normally shelf-stable products.
Computer Vision and Deep Learning for Environment-Adaptive Control of Robotic Lower-Limb Exoskeletons

Robotic exoskeletons require human control and decision making to switch between different locomotion modes, which can be inconvenient and cognitively demanding. To support the development of automated locomotion mode recognition systems (i.e., high-level controllers), we designed an environment recognition system using computer vision and deep learning. We collected over 5.6 million images of indoor and outdoor real-world walking environments using a wearable camera system, of which ~923,000 images were annotated using a 12-class hierarchical labelling architecture (called the ExoNet database). We then trained and tested the EfficientNetB0 convolutional neural network, designed for efficiency using neural architecture search, to predict the different walking environments. Our environment recognition system achieved ~73% image classification accuracy. While these preliminary results benchmark Efficient-NetB0 on the ExoNet database, further research is needed to compare different image classification algorithms to develop an accurate and real-time environment-adaptive locomotion mode recognition system for robotic exoskeleton control.
Heterogeneous non-canonical nucleosomes predominate in yeast cells in situ

Nuclear processes depend on the organization of chromatin, whose basic units are cylinder-shaped complexes called nucleosomes. A subset of mammalian nucleosomes in situ (inside cells) resembles the canonical structure determined in vitro 25 years ago. Nucleosome structure in situ is otherwise poorly understood. Using cryo-ET and 3-D classification analysis of budding yeast cells, here we find that canonical nucleosomes account for less than 10% of total nucleosomes expected in situ. In a strain in which H2A-GFP is the sole source of histone H2A, class averages that resemble canonical nucleosomes both with and without GFP densities are found ex vivo (in nuclear lysates), but not in situ. These data suggest that the budding yeast intranuclear environment favors multiple non-canonical nucleosome conformations. Using the structural observations here and the results of previous genomics and biochemical studies, we propose a model in which the average budding yeast nucleosome’s DNA is partially detached in situ.
Dynamics of data availability in disease modeling: An example evaluating the trade-offs of ultra-fine-scale factors applied to human West Nile virus disease models in the Chicago area, USA

Background Since 1999, West Nile virus (WNV) has moved rapidly across the United States, resulting in tens of thousands of human cases. Both the number of human cases and the minimum infection rate (MIR) in vector mosquitoes vary across time and space and are driven by numerous abiotic and biotic forces, ranging from differences in microclimates to socio-demographic factors. Because the interactions among these multiple factors affect the locally variable risk of WNV illness, it has been especially difficult to model human disease risk across varying spatial and temporal scales. Cook and DuPage Counties, comprising the city of Chicago and surrounding suburbs, experience some of the highest numbers of human neuroinvasive cases of WNV in the United States. Despite active mosquito control efforts, there is consistent annual WNV presence, resulting in more than 285 confirmed WNV human cases and 20 deaths from the years 2014-2018 in Cook County alone. Methods A previous Chicago-area WNV model identified the fifty-five most high and low risk locations in the Northwest Mosquito Abatement District (NWMAD), an enclave ¼ the size of the combined Cook and DuPage county area. In these locations, human WNV risk was stratified by model performance, as indicated by differences in studentized residuals. Within these areas, an additional two-years of field collections and data processing was added to a 12-year WNV dataset that includes human cases, MIR, vector abundance, and land-use, historical climate, and socio-economic and demographic variables, and was assessed by an ultra-fine-scale (1 km spatial × 1 week temporal resolution) multivariate logistic regression model. Results Multivariate statistical methods applied to the ultra-fine-scale model identified fewer explanatory variables while improving upon the fit of the previous model. Beyond MIR and climatic factors, efforts to acquire additional covariates only slightly improved model predictive performance. Conclusions These results suggest human WNV illness in the Chicago area may be associated with fewer, but increasingly critical, key variables at finer scales. Given limited resources, these findings suggest large variations in model performance occur, depending on covariate availability, and provide guidance in variable selection for optimal WNV human illness modeling.
Structural insights into the activation of human calcium-sensing receptor

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that maintains Ca2+ homeostasis in serum. Here, we present the cryo-electron microscopy structures of the CaSR in the inactive and active states. Complemented with previously reported crystal structures of CaSR extracellular domains, it suggests that there are three distinct conformations: inactive, intermediate and active state during the activation. We used a negative allosteric nanobody to stabilize the CaSR in the fully inactive state and found a new binding site for Ca2+ ion that acts as a composite agonist with L-amino acid to stabilize the closure of active Venus flytraps. Our data shows that the agonist binding leads to the compaction of the dimer, the proximity of the cysteine-rich domains, the large-scale transitions of 7-transmembrane domains, and the inter-and intrasubunit conformational changes of 7-transmembrane domains to accommodate the downstream transducers. Our results reveal the structural basis for activation mechanisms of the CaSR.