Miracle-dz/UniFAR-FTUs huggingface dataset:
A robust voice-selective response in the human brain as revealed by electrophysiological recordings and fast periodic auditory stimulation

Voices are arguably among the most relevant sounds in humans’ everyday life, and several studies have suggested the existence of voice-selective regions in the human brain. Despite two decades of research, defining the human brain regions supporting voice recognition remains challenging. Moreover, whether neural selectivity to voices is merely driven by acoustic properties specific to human voices (e.g. spectrogram, harmonicity), or whether it also reflects a higher-level categorization response is still under debate. Here, we objectively measured rapid automatic categorization responses to human voices with Fast Periodic Auditory Stimulation (FPAS) combined with electroencephalography (EEG). Participants were tested with stimulation sequences containing heterogeneous non-vocal sounds from different categories presented at 4 Hz (i.e., 4 stimuli/second), with vocal sounds appearing every 3 stimuli (1.333 Hz). A few minutes of stimulation are sufficient to elicit robust 1.333 Hz voice-selective focal brain responses over superior temporal regions of individual participants. This response is virtually absent for sequences using frequency-scrambled sounds, but is clearly observed when voices are presented among sounds from musical instruments matched for pitch and harmonicity-to-noise ratio. Overall, our FPAS paradigm demonstrates that the human brain seamlessly categorizes human voices when compared to other sounds including matched musical instruments and that voice-selective responses are at least partially independent from low-level acoustic features, making it a powerful and versatile tool to understand human auditory categorization in general. Significance statement Voices are arguably among the most relevant sounds we hear in our everyday life, and several studies have corroborated the existence of regions in the human brain that respond preferentially to voices. However, whether this preference is driven by specific acoustic properties of voices or if it rather reflects a higher-level categorization response to voices is still under debate. We propose a new approach to objectively identify rapid automatic voice-selective responses with frequency tagging and electroencephalographic recordings. In four minutes of recording only, we recorded robust voice-selective responses independent from low-level acoustic cues, making this approach highly promising for studying auditory perception in children and clinical populations.
Eukaryotic initiation factor EIF-3.G augments mRNA translation efficiency to regulate neuronal activity

The translation initiation complex eIF3 imparts specialized functions to regulate protein expression. However, understanding of eIF3 activities in neurons remains limited despite widespread dysregulation of eIF3 subunits in neurological disorders. Here, we report a selective role of the C. elegans RNA-binding subunit EIF-3.G in shaping the neuronal protein landscape. We identify a missense mutation in the conserved Zinc-Finger (ZF) of EIF-3.G that acts in a gain-of-function manner to dampen neuronal hyperexcitation. Using neuron type-specific seCLIP, we systematically mapped EIF-3.G-mRNA interactions and identified EIF-3.G occupancy on GC-rich 5′UTRs of a select set of mRNAs enriched in activity-dependent functions. We demonstrate that the ZF mutation in EIF-3.G alters translation in a 5′UTR dependent manner. Our study reveals an in vivo mechanism for eIF3 in governing neuronal protein levels to control activity states and offers insights into how eIF3 dysregulation contributes to neuronal disorders.
A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission

A malaria parasite plasma membrane phospholipid flippase protects ookinetes in mosquito midgut epithelium for transmission. Mosquito midgut epithelium traversal is essential for malaria parasite transmission. Phospholipid flippases are eukaryotic type 4 P-type adenosine triphosphatases (P4-ATPases), which, in association with CDC50, translocate phospholipids across the membrane lipid bilayers. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasite Plasmodium yoelii. Disruption of ATP7 blocks the parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are capable of invading the midgut, they are eliminated within the epithelial cells by a process independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase cofactor CDC50C. Depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to uptake phosphatidylcholine across the plasma membrane. Ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifies Plasmodium flippase as a mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.
Borrelia infection in rodent host has dramatic effects on the microbiome of ticks

Background Vector-borne diseases remain major causes of human morbidity and mortality. It is increasingly recognized that the community of microbes inhabiting arthropods can strongly affect their vector competence, but the role of the tick microbiome in Borrelia transmission – the cause of Lyme disease – remains unclear. Results Here, we use a large-scale experiment to clarify the reciprocal interactions between Borrelia afzelii and the microbiome of Ixodes ricinus, its primary vector. In contrast to other reports, we find that depletion of the bacterial microbiome in larval ticks has no effect on their subsequent acquisition of B. afzelii during blood feeding on infected mice. Rather, exposure to B. afzelii-infected hosts drives pervasive changes to the tick microbiome, decreasing overall bacterial abundance, shifting bacterial community composition, and increasing bacterial diversity. These effects appear to be independent of the acquisition of B. afzelii by ticks, suggesting they are mediated by physiological or immunological aspects of B. afzelii infection in the rodent host. Conclusions Manipulation of the microbiome of I. ricinus larvae had no effect on their ability to acquire B. afzelii. In contrast, B. afzelii infection in the mouse had dramatic effects on the composition of the gut microbiome in I. ricinus nymphs. Our study demonstrates that vector-borne infections in the vertebrate host shape the microbiome of the arthropod vector.
Hülle-cell-mediated protection of fungal reproductive and overwintering structures against fungivorous animals

Fungal Hülle cells with nuclear storage and developmental backup functions are reminiscent of multipotent stem cells. In the soil, Hülle cells nurse the overwintering fruiting bodies of Aspergillus nidulans. The genome of A. nidulans harbors genes for the biosynthesis of xanthones. We show that enzymes and metabolites of this biosynthetic pathway accumulate in Hülle cells under the control of the regulatory velvet complex, which coordinates development and secondary metabolism. Deletion strains blocked in the conversion of anthraquinones to xanthones are delayed in maturation and growth of fruiting bodies. Xanthones are not required for sexual development but exert antifeedant effects on fungivorous animals such as springtails and woodlice. These findings reveal a novel role of Hülle cells in establishing secure niches for A. nidulans by accumulating metabolites with antifeedant activity that protect reproductive structures from animal predators.
Good host - bad host: molecular and evolutionary basis for survival, its failure, and virulence factors of the zoonotic nematode Anisakis pegreffii

Parasitism is a highly successful life strategy and a driving force in genetic diversity that has evolved many times over. Consequently, parasitic organisms have adopted a rich display of traits associated with survival that guarantees an effective “communication” with the host immunity and a balance with surrounding microbiome. However, gain/loss of hosts along the evolutionary axis represents a complex scenario that as contemporary onlookers, we can observe only after a long time displacement. The zoonotic and monophyletic Anisakidae diverged from its terrestrial sister group Ascarididae 150-250 Ma, although a split from their common ancestral host, a terrestrial amniote, seemingly happened already in Early Carboniferous (360.47 Ma). Faced with the sea-level rise during the Permian-Triassic extinction (215 Ma), anisakids acquired a semiaquatic tetrapod host, and as a result of lateral host-switches in Cenozoic, colonised marine mammals, co-evolving with their “new hosts”. Although contemporary anisakids have lost the ability to propagate in terrestrial hosts, they can survive for a limited time in humans. To scrutinize anisakid versatility to infect evolutionary-distant host, we performed transcriptomic profiling of larvae infecting the accidental host (rat) and compared it to that of larvae infecting an evolutionary-familiar, paratenic host (fish). Identified differences and the modeling of handful of shared transcripts, provides the first insights into evolution of larval nematode virulence, warranting further investigation of shared transcript as potential drug therapy targets. Our findings have also revealed some key intrinsic cues that direct larval fate during infection.
A General LSTM-based Deep Learning Method for Estimating Neuronal Models and Inferring Neural Circuitry

Computational neural models are essential tools for neuroscientists to study the functional roles of single neurons or neural circuits. With the recent advances in experimental techniques, there is a growing demand to build up neural models at single neuron or large-scale circuit levels. A long-standing challenge to build up such models lies in tuning the free parameters of the models to closely reproduce experimental recordings. There are many advanced machine-learning-based methods developed recently for parameter tuning, but many of them are task-specific or requires onerous manual interference. There lacks a general and fully-automated method since now. Here, we present a Long Short-Term Memory (LSTM)-based deep learning method, General Neural Estimator (GNE), to fully automate the parameter tuning procedure, which can be directly applied to both single neuronal models and large-scale neural circuits. We made comprehensive comparisons with many advanced methods, and GNE showed outstanding performance on both synthesized data and experimental data. Finally, we proposed a roadmap centered on GNE to help guide neuroscientists to computationally reconstruct single neurons and neural circuits, which might inspire future brain reconstruction techniques and corresponding experimental design. The code of our work will be publicly available upon acceptance of this paper.
Age-related increase in matrix stiffness downregulates α-Klotho in chondrocytes and induces cartilage degeneration

Enhanced mechanistic insight into age-related knee osteoarthritis (KOA) is an essential step to promote successful translation of animal research to bedside interventions. To this end, the goal of these studies was to interrogate molecular mechanisms driving age-related KOA in a mouse model and correspond findings to human knee cartilage. Unbiased mass spectrometry proteomics of cartilage tissue revealed PI3K/Akt signaling was the predominant pathway disrupted over time in male, but not female, mice. This finding was consistent with a significantly accelerated KOA progression in males when compared to female counterparts. In probing for upstream regulators of these age-dependent alterations, we found that α-Klotho, a suppressor of PI3K/Akt signaling and potent longevity protein, significantly decreased with aging in both mouse and human knee cartilage. Upstream of these alterations, we found that age-related increases in matrix stiffness initiated a cascade of altered nuclear morphology and downregulated α-Klotho expression, ultimately impairing chondrocyte health. Conversely, reducing matrix stiffness increased α-Klotho expression in chondrocytes, thus enhancing their chondrogencity and cartilage integrity. Collectively, our findings establish a novel mechanistic link between age-related alterations in ECM biophysical properties and regulation of cartilage health by α-Klotho.
A structure-derived mechanism reveals how capping protein promotes nucleation in branched actin networks

Heterodimeric capping protein (CP/CapZ) is an essential factor for the assembly of branched actin networks, which push against cellular membranes to drive a large variety of cellular processes. Aside from terminating filament growth, CP stimulates the nucleation of actin filaments by the Arp2/3 complex in branched actin networks through an unclear mechanism. Here, we report the structure of capped actin filament barbed ends, which reveals how CP not only prevents filament elongation, but also controls access to both terminal filament subunits. In addition to its primary binding site that blocks the penultimate subunit, we find that the CP sterically occludes the central interaction site of the terminal actin protomer through one of its C-terminal “tentacle” extensions. Deletion of this β tentacle only modestly impairs capping. However in the context of a growing branched actin network, its removal potently inhibits nucleation promoting factors (NPFs) by tethering them to capped filament ends. End tethering of NPFs prevents their loading with actin monomers required for activation of the Arp2/3 complex and thus strongly inhibits branched network assembly both in cells and reconstituted motility assays. Our results mechanistically explain how CP couples two opposed processes –capping and nucleation– in branched actin network assembly.
Wrack enhancement of post-hurricane vegetation and geomorphological recovery in a coastal dune

Coastal ecosystems such as sand dunes, mangrove forests, and salt marshes provide natural storm protection for vulnerable shorelines. At the same time, storms erode and redistribute biological materials among coastal systems via wrack. Yet how such cross-ecosystem subsidies affect post-storm recovery is not well understood. Here, we report an experimental investigation into the effect of storm wrack on eco-geomorphological recovery of a coastal embryo dune in north-eastern Florida, USA, following hurricane Irma. We contrasted replicated 100-m2 wrack-removal and unmanipulated (control) plots, measuring vegetation and geomorphological responses over 21 months. Relative to controls, grass cover was reduced 4-fold where diverse storm wrack, including seagrass rhizomes, seaweed, and wood, was removed. Wrack removal was also associated with a reduction in mean elevation, which persisted until the end of the experiment when removal plots had a 14% lower mean elevation compared to control plots. These results suggest that subsides of wrack re-distributed from other ecosystem types (e.g. seagrasses, macroalgae, uplands): i) enhances the growth of certain dune-building grasses; and ii) boosts the geomorphological recovery of coastal dunes. Our study also indicates that the practice of post-storm beach cleaning to remove wrack – a practice widespread outside of protected areas – may undermine the resilience of coastal dunes and their services.
DNA Methylation Networks Underlying Mammalian Traits

Epigenetics has hitherto been studied and understood largely at the level of individual organisms. Here, we report a multi-faceted investigation of DNA methylation across 11,117 samples from 176 different species. We performed an unbiased clustering of individual cytosines into 55 modules and identified 31 modules related to primary traits including age, species lifespan, sex, adult species weight, tissue type and phylogenetic order. Analysis of the correlation between DNA methylation and species allowed us to construct phyloepigenetic trees for different tissues that parallel the phylogenetic tree. In addition, while some stable cytosines reflect phylogenetic signatures, others relate to age and lifespan, and in many cases responding to anti-aging interventions in mice such as caloric restriction and ablation of growth hormone receptors. Insights uncovered by this investigation have important implications for our understanding of the role of epigenetics in mammalian evolution, aging and lifespan.
VASP-mediated actin dynamics activate and recruit a filopodia myosin

Filopodia are thin, actin-based structures that cells use to interact with their environments. Filopodia initiation requires a suite of conserved proteins but the mechanism remains poorly understood. The actin polymerase VASP and a MyTH-FERM (MF) myosin, DdMyo7 in amoeba, are essential for filopodia initiation. DdMyo7 is localized to dynamic regions of the actin-rich cortex. Analysis of VASP mutants and treatment of cells with anti-actin drugs shows that myosin recruitment and activation in Dictyostelium requires localized VASP-dependent actin polymerization. Targeting of DdMyo7 to the cortex alone is not sufficient for filopodia initiation; VASP activity is also required. The actin regulator locally produces a cortical actin network that activates myosin and together they shape the actin network to promote extension of parallel bundles of actin during filopodia formation. This work reveals how filopodia initiation requires close collaboration between an actin binding protein, the state of the actin cytoskeleton and MF myosin activity.
Face processing of social cognition in patients with first episode psychosis: Its deficits and association with the right subcallosal anterior cingulate cortex

The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 79 FEP patients and 80 healthy controls (HCs). We looked for a possible correlation between face processing and multimodal MRI characteristics such as resting-state functional connectivity (rsFC) and brain volume. We observed worse recognition accuracy, longer recognition response time, and longer memory response time in FEP patients when compared with HCs. Of these, memory response time was selectively correlated with specific rsFCs, which included the right subcallosal sub-region of BA24 in the ACC (scACC), only in FEP patients. The volume of this region was also correlated with memory response time in FEP patients. The scACC is functionally and structurally important in FEP-associated abnormalities of face processing measures in social cognition.
Svep1 stabilises developmental vascular anastomosis in reduced flow conditions

ABSTRACT Molecular mechanisms controlling the formation, stabilisation and maintenance of blood vessel connections remain poorly defined. Here, we identify blood flow and the large extracellular protein Svep1 as co-modulators of vessel anastomosis during developmental angiogenesis in zebrafish embryos. Both loss of Svep1 and blood flow reduction contribute to defective anastomosis of intersegmental vessels. The reduced formation and lumenisation of the dorsal longitudinal anastomotic vessel (DLAV) is associated with a compensatory increase in Vegfa/Vegfr pERK signalling, concomittant expansion of apelin-positive tip cells, but reduced expression of klf2a. Experimentally, further increasing Vegfa/Vegfr signalling can rescue the DLAV formation and lumenisation defects, whereas its inhibition dramatically exacerbates the loss of connectivity. Mechanistically, our results suggest that flow and Svep1 co-regulate the stabilisation of vascular connections, in part by modulating the Vegfa/Vegfr signalling pathway.
Intergenerational niche differentiation in filmy ferns (Hy- menophyllaceae)

Desiccation tolerancewas a key trait that allowed plants to colonize land. However, little is known about the transition from desiccation tolerant non-vascular plants to desiccation sensitive vascular ones. Filmy ferns (Hymenophyllaceae) represent a useful system to investigate how water-stress strategies differ between non-vascular and vascular stages within a single organism because they have vascularized sporophytes and nonvascular
Pyrolyzed Substrates Induce Aromatic Compound Metabolism in the Post-fire Fungus, Pyronema domesticum

Wildfires represent a fundamental and profound disturbance in many ecosystems, and their frequency and severity are increasing in many regions of the world. Fire affects soil by removing carbon in the form of CO2 and transforming remaining surface carbon into pyrolyzed organic material (PyOM). Fires also generate substantial necromass at depths where the heat kills soil organisms but does not catalyze the formation of PyOM. Pyronema species strongly dominate soil fungal communities within weeks to months after fire. However, the carbon pool (i.e. necromass or PyOM) that fuels their rise in abundance is unknown. We used a Pyronema domesticum isolate from the catastrophic 2013 Rim Fire (CA, USA) to ask if P. domesticum is capable of metabolizing PyOM. P. domesticum grew readily on agar media where the sole carbon source was PyOM (specifically, pine wood PyOM produced at 750 °C). Using RNAseq, we investigated the response of P. domesticum to PyOM and observed a comprehensive induction of genes involved in the metabolism and mineralization of aromatic compounds, typical of those found in PyOM. Lastly, we used 13C-labeled 750 °C PyOM to demonstrate that P. domesticum is capable of mineralizing PyOM to CO2. Collectively, our results indicate a robust potential for P. domesticum to liberate carbon from PyOM in post-fire ecosystems and return it to the bioavailable carbon pool. IMPORTANCE Fires are increasing in frequency and severity in many regions across the world. Thus, it’s critically important to understand how our ecosystems respond to inform restoration and recovery efforts. Fire transforms the soil, removing many nutrients while leaving behind both nutritious necromass and complex pyrolyzed organic matter, which is often recalcitrant. Filamentous fungi of the genus Pyronema strongly dominate soil fungal communities soon after fire. While Pyronema are key pioneer species in post-fire environments, the nutrient source that fuels their rise in abundance is unknown. In this manuscript, we used a P. domesticum isolate from the catastrophic 2013 Rim Fire (CA, USA) to demonstrate that P. domesticum metabolizes pyrolyzed organic material, effectively liberating this complex pyrolyzed carbon and returning it to the bioavailable carbon pool. The success of Pyronema in post-fire ecosystems has the potential to kick-start growth of other organisms and influence the entire trajectory of post-fire recovery.