Miracle-dz/UniFAR-FTUs huggingface dataset:
Preference for animate domain sounds in the fusiform gyrus of blind individuals is modulated by shape-action mapping

In high-level visual shape areas in the human brain, preference for inanimate objects is observed regardless of stimulation modality (visual/auditory/tactile) and subjects’ visual experience (sighted/blind individuals), whereas preference for animate entities seems robust only in the visual modality. Here, we test a hypothesis explaining this effect: visual shape representations can be reliably activated through different sensory modalities only when they systematically map onto action system computations. We studied fMRI activations in congenitally blind and sighted subjects listening to animal, object, and human sounds. We found that face shape areas in blind individuals preferentially respond to human facial expression sounds, with transparent face shape/motor representation mapping, but not to speech or animal sounds. Using face areas’ activation, we could distinguish facial expressions from other sounds in both groups. We conclude that auditory stimulation can activate visual shape representation of those stimuli – inanimate or animate - for which shape-action mapping is transparent.
Prioritization of osteoporosis-associated GWAS SNPs using epigenomics and transcriptomics

Genetic risk factors for osteoporosis, a prevalent disease associated with aging, have been examined in many genome-wide association studies (GWAS). A major challenge is to prioritize transcription-regulatory GWAS-derived variants that are likely to be functional. Given the critical role of epigenetics in gene regulation, we have used an unusual epigenetics- and transcription-based approach to identify credible regulatory SNPs relevant to osteoporosis from 38 reported BMD GWAS. Using Roadmap databases, we prioritized SNPs based upon their overlap with strong enhancer or promoter chromatin preferentially in osteoblasts relative to 11 heterologous cell culture types. The selected SNPs also had to overlap open chromatin (DNaseI-hypersensitive sites) and DNA sequences predicted to bind to osteoblast-relevant transcription factors in an allele-specific manner. From >50,000 GWAS-derived SNPs, we identified 16 novel and credible regulatory SNPs (Tier-1 SNPs) for osteoporosis risk. Their associated genes, BICC1, LGR4, DAAM2, NPR3, or HMGA2, are involved in osteoblastogenesis or bone homeostasis and regulate cell signaling or enhancer function. Four of them are preferentially expressed in osteoblasts. BICC1, LGR4, and DAAM2 play important roles in canonical Wnt signaling, a pathway critical to bone formation and repair. The transcription factors that are predicted to bind to the Tier-1 SNP-containing DNA sequences also have bone-related functions. For the seven Tier-1 SNPs near the 5’ end of BICC1, examination of eQTL overlap and the distribution of BMD-increasing alleles suggests that at least one SNP in each of two clusters contributes to inherited osteoporosis risk. Our study not only illustrates a method that can be used to identify novel BMD-related causal regulatory SNPs for future study, but also reveals evidence that some of the Tier-1 SNPs exert their effects on BMD risk indirectly through little-studied noncoding RNA genes, which in turn may control the nearby bone-related protein-encoding gene.
Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes

Levels of sex differences for human body size and shape phenotypes are hypothesized to have adaptively reduced following the adoption of agriculture. In this study, we tested this hypothesis by first identifying thousands of single nucleotide polymorphisms (SNPs) that differentially impact trait variation between British females and males for five phenotypes: height, body mass, hip circumference, body fat percentage, and waist circumference. After confirming the biological plausibility of these SNPs, we then used a population genomic approach to study the recent (within the last 3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. We observed significant increases in the frequencies of alleles associated with greater body fat percentage in females (P=0.0038; FDR=0.038), directionally opposite to that predicted by the sex differentiation reduction hypothesis. Otherwise, we found no evidence of positive selection for sex difference-associated alleles for any other trait. Overall, our results challenge the longstanding hypothesis that sex differences adaptively decreased following subsistence transitions from hunting and gathering to agriculture.
Transferability of Brain decoding using Graph Convolutional Networks

Transfer learning has been a very active research topic in natural image processing. But few studies have reported notable benefits of transfer learning on medical imaging. In this study, we sought to investigate the transferability of deep artificial neural networks (DNN) in brain decoding, i.e. inferring brain state using fMRI brain response over a short window. Instead of using pretrained models from ImageNet, we trained our base model on a large-scale neuroimaging dataset using graph convolutional networks (GCN). The transferability of learned graph representations were evaluated under different circumstances, including knowledge transfer across cognitive domains, between different groups of subjects, and among different sites using distinct scanning sequences. We observed a significant performance boost via transfer learning either from the same cognitive domain or from other task domains. But the transferability was highly impacted by the scanner site effect. Specifically, for datasets acquired from the same site using the same scanning sequences, using transferred features highly improved the decoding performance. By contrast, the transferability of representations highly decreased between different sites, with the performance boost reducing from 20% down to 7% for the Motor task and decreasing from 15% to 5% for Working-memory tasks. Our results indicate that in contrast to natural images, the scanning condition, instead of task domain, has a larger impact on feature transfer for medical imaging. With other advanced tools such as layer-wise fine-tuning, the decoding performance can be further improved through learning more site-specific high-level features while retaining the transferred low-level representations of brain dynamics.
The mechanisms behind perivascular fluid flow

Flow of cerebrospinal fluid (CSF) in perivascular spaces (PVS) is one of the key concepts involved in theories concerning clearance from the brain. Experimental studies have demonstrated both net and oscillatory movement of microspheres in PVS (Mestre et al. (2018), Bedussi et al. (2018)). The oscillatory particle movement has a clear cardiac component, while the mechanisms involved in net movement remain disputed. Using computational fluid dynamics, we computed the CSF velocity and pressure in a PVS surrounding a cerebral artery subject to different forces, representing arterial wall expansion, systemic CSF pressure changes and rigid motions of the artery. The arterial wall expansion generated velocity amplitudes of 60–260 µm/s, which is in the upper range of previously observed values. In the absence of a static pressure gradient, predicted net flow velocities were small (<0.5 µm/s), though reaching up to 7 µm/s for non-physiological PVS lengths. In realistic geometries, a static systemic pressure increase of physiologically plausible magnitude was sufficient to induce net flow velocities of 20–30 µm/s. Moreover, rigid motions of the artery added to the complexity of flow patterns in the PVS. Our study demonstrates that the combination of arterial wall expansion, rigid motions and a static CSF pressure gradient generates net and oscillatory PVS flow, quantitatively comparable with experimental findings. The static CSF pressure gradient required for net flow is small, suggesting that its origin is yet to be determined. Significance Statement Cerebrospinal fluid flow along perivascular spaces is hypothesized to be instrumental for clearance of metabolic waste from the brain, such as e.g. clearance of amyloid-beta, a protein known to accumulate as plaque within the brain in Alzheimer’s patients. Arterial pulsations have been proposed as the main driving mechanism for perivascular fluid flow, but it is unclear whether this mechanism alone is sufficient. Our results show that arterial pulsations drive oscillatory movement in perivascular spaces, but also indicate that a pressure gradient is required for net flow. However, the required pressure gradient is relatively small, thus suggesting that its origins can be associated with physiological processes within the brain and/or experimental procedures.
PCNA antagonizes cohesin-dependent roles in genomic stability

PCNA sliding clamp binds factors through which histone deposition, chromatin remodeling, and DNA repair are coupled to DNA replication. PCNA also directly binds Eco1/Ctf7 acetyltransferase, which in turn activates cohesins and establishes cohesion between nascent sister chromatids. While increased recruitment thus explains the mechanism through which elevated levels of chromatin-bound PCNA rescue eco1 mutant cell growth, the mechanism through which PCNA instead worsens cohesin mutant cell growth remains unknown. Possibilities include that elevated levels of long-lived chromatin-bound PCNA reduce either cohesin deposition onto DNA or cohesin acetylation. Instead, our results reveal that PCNA increases the levels of both chromatin-bound cohesin and cohesin acetylation. Beyond sister chromatid cohesion, PCNA also plays a critical role genomic stability such that high levels of chromatin-bound PCNA destabilize the DNA replication fork. At a relatively modest increase of chromatin-bound PCNA, however, fork stability and progression appear normal in wildtype cells. Our results reveal that even this moderate increase of PCNA sensitizes cohesin mutant cells to DNA damaging agents and in a process that involves the DNA damage response kinase Mec1(ATR), but not Tel1(ATM). These and other findings document that PCNA mis-regulation results in genome instabilities that normally are resolved by cohesin and suggest that elevating levels of chromatin-bound PCNA may target cohesinopathic cells linked to cancer.
Team Flow Is a Unique Brain State Associated with Enhanced Information Integration and Interbrain Synchrony

Visual Abstract Team flow occurs when a group functions in a high task engagement to achieve a goal, commonly seen in performance and sports. Team flow can enable enhanced positive experiences, as compared with individual flow or regular socializing. However, the neural basis for this enhanced behavioral state remains unclear. Here, we identified neural correlates (NCs) of team flow in human participants using a music rhythm task with electroencephalogram hyperscanning. Experimental manipulations held the motor task constant while disrupting the corresponding hedonic music to interfere with the flow state or occluding the partner’s positive feedback to impede team interaction. We validated these manipulations by using psychometric ratings and an objective measure for the depth of flow experience, which uses the auditory-evoked potential (AEP) of a task-irrelevant stimulus. Spectral power analysis at both the scalp sensors and anatomic source levels revealed higher β-γ power specific to team flow in the left middle temporal cortex (L-MTC). Causal interaction analysis revealed that the L-MTC is downstream in information processing and receives information from areas encoding the flow or social states. The L-MTC significantly contributes to integrating information. Moreover, we found that team flow enhances global interbrain integrated information (II) and neural synchrony. We conclude that the NCs of team flow induce a distinct brain state. Our results suggest a neurocognitive mechanism to create this unique experience.
Study on seed morphometry of seven threatened Himalayan orchids exhibiting varied life modes

Abstract A study was conducted on seed morphometry of seven threatened Himalayan orchids (listed in Appendix II of CITES) belonging to three different subfamilies, and exhibiting terrestrial (Arundina graminifolia, Cypripedium cordigerum, Habenaria marginata, Herminium monorchis), mycoheterotrophic (Gastrodia falconeri) or epiphytic (Aerides multiflora, Pholidota articulata) life modes. Seeds were fusiform, filiform or ovoid in shape and their size showed direct correlation with plant habit. They were relatively smaller in epiphytes than their terrestrial or mycoheterotrophic counterparts. Seeds were truncated except in Arundina graminifolia (l/w > 6.0). Scanning electron micrographs revealed that the testa cells were longitudinally oriented, arranged either straight or in a spiral, and their periclinal walls were comparatively irregularly placed in epiphytic species. The wall thickenings were also more pronounced in epiphytes. Embryos were tiny and most of the seed space (even > 90% in Pholidota articulata and Gastrodia falconeri) was occupied by air. Highest seed to embryo (s/e) volume ratio (17.94) was recorded in Pholidota articulata, and lowest (2.14) was in Arundina graminifolia. Though the orchids producing seeds with higher s/e volume ratio and higher percentage of air space find wider distribution, the localized distribution of Gastrodia falconeri (mycoheterotroph) seems to be related to its complex nutritional requirements.
Homeostatic Plasticity Requires Remodeling of the Homer-Shank Interactome

Neurons maintain constant levels of excitability using homeostatic scaling, which adjusts relative synaptic strength in response to large changes in overall activity. It is still unknown how homeostatic scaling affects network-level protein interactions in the synapse despite extensive reporting of individual scaling-associated transcriptomic and proteomic changes. Here, we assessed a glutamatergic synapse protein interaction network (PIN) composed of 380 binary interactions among 21 protein members to identify protein complexes altered by synaptic scaling in vitro and in vivo. In cultured cortical neurons, we observed widespread bidirectional PIN alterations during up- and downscaling that reflected rapid glutamate receptor shuttling via synaptic scaffold remodeling. Sensory deprivation of the barrel cortex caused a PIN response that reflected changes in mGluR tone and NMDAR-dependent metaplasticity, consistent with emerging models of homeostatic plasticity in the barrel cortex that restore excitatory/inhibitory balance. Mice lacking Homer1 or Shank3B did not undergo normal PIN rearrangements, suggesting that these Autism Spectrum Disorder (ASD)-linked proteins serve as structural hubs for synaptic homeostasis. Our approach demonstrates how changes in the protein content of synapses during homeostatic plasticity translate into functional PIN alterations that mediate changes in neuron excitability.
Identification of amino acid residues important for assembly of GABAA receptor α1 and γ2 subunits

Comparative models of GABAA receptors composed of α1β3γ2 subunits were generated using the acetylcholine‐binding protein (AChBP) as a template and were used for predicting putative engineered cross‐link sites between the α1 and the γ2 subunit. The respective amino acid residues were substituted by cysteines and disulfide bond formation between subunits was investigated on co‐transfection into human embryonic kidney (HEK) cells. Although disulfide bond formation between subunits could not be observed, results indicated that mutations studied influenced assembly of GABAA receptors. Whereas residue α1A108 was important for the formation of assembly intermediates with β3 and γ2 subunits consistent with its proposed location at the α1(+) side of GABAA receptors, residues γ2T125 and γ2P127 were important for assembly with β3 subunits. Mutation of each of these residues also caused an impaired expression of receptors at the cell surface. In contrast, mutated residues α1F99C, α1S106C or γ2T126C only impaired the formation of receptors at the cell surface when co‐expressed with subunits in which their predicted interaction partner was also mutated. These data are consistent with the prediction that the mutated residue pairs are located close to each other.
Xyloglucan remodelling defines differential tissue expansion in plants

1 Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences Vienna (BOKU), Muthgasse 18, 1190 Vienna, Austria. Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark. Institute of Science and Technology Austria, Klosterneuburg, 3400, Austria. Department of Forest Genetics and Plant Physiology, Umeå Plant Science Centre, Swedish University of Agricultural Sciences, SE-901 87 Umeå, Sweden. Laboratory of Growth Regulators, Faculty of Science, Palacký University and Institute of Experimental Botany, The Czech Academy of Sciences, Šlechtitelů 27, Olomouc, Czech Republic Institut Jean-Pierre Bourgin, Institut National de la Recherche Agronomique, AgroParisTech, CNRS, Université Paris-Saclay, 78000 Versailles, France. § Equal contributions *Correspondence and requests for materials should be addressed to J.K. -V.
α-Synuclein facilitates endocytosis by elevating the steady-state levels of phosphatidylinositol 4,5-bisphosphate

α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson’s disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we have investigated the role of α-Syn in membrane trafficking through its association with acidic phosphoinositides (PIPs), such as phosphatidylinositol 4,5-bisphosphate (PI4,5P2) and phosphatidylinositol 3,4-bisphosphate (PI3,4P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor AP2 at clathrin-coated pits. Using endocytosis of transferrin, an indicator of clathrin mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI4,5P2 levels. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by α-Syn mutations. In accord with their effects on PI4,5P2 levels at the plasma membrane, the PD associated E46K and A53T mutations further enhance SV endocytosis. However, neither A30P mutation, nor Lysine to Glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, that interfere with phospholipid binding, affect SV endocytosis. This study provides evidence for a critical involvement of PIPs in α-Syn-mediated membrane trafficking. Significance Statement α-Synuclein (α-Syn) protein is known for its causative role in Parkinson’s disease. α-Syn is normally involved in mechanisms of membrane trafficking, including endocytosis, exocytosis and synaptic vesicles cycling. However, a certain degree of controversy regarding the exact role of α-Syn in these mechanisms persists. Here we show that α-Syn acts to increase plasma membrane levels PI4,5P2 and PI3,4P2 to facilitate clathrin mediated and synaptic vesicles endocytosis. Based on the results, we suggest that α-Syn interactions with the acidic phosphoinositides facilitate a shift in their homeostasis to support endocytosis.
Combined transient ablation and single cell RNA sequencing reveals the development of medullary thymic epithelial cells

Medullary thymic epithelial cells (mTECs) play a critical role in central immune tolerance by mediating negative selection of autoreactive T cells through the collective expression of the peripheral self-antigen compartment, including tissue-specific antigens (TSAs). Recent work has shown that gene expression patterns within the mTEC compartment are remarkably heterogenous and include multiple differentiated cell states. To further define mTEC development and medullary epithelial lineage relationships, we combined lineage tracing and recovery from transient in vivo mTEC ablation with single cell RNA-sequencing. The combination of bioinformatic and experimental approaches revealed a non-stem transit-amplifying population of cycling mTECs that preceded Aire expression. Based on our findings, we propose a branching model of mTEC development wherein a heterogeneous pool of transit-amplifying cells gives rise to Aire- and Ccl21a-expressing mTEC subsets. We further use experimental techniques to show that within the Aire-expressing developmental branch, TSA expression peaked as Aire expression decreased, implying Aire expression must be established before TSA expression can occur. Collectively, these data provide a higher order roadmap of mTEC development and demonstrate the power of combinatorial approaches leveraging both in vivo models and high-dimensional datasets.
Root Herbivores in an Orchard System: Assessing the Influence of Root Herbivory and Pest Management on Root Dynamics, Soil Fauna, and Soil Carbon Pools

The central objective of our study was to assess the influence of root herbivory on root dynamics and major components of soil carbon cycles. A closely related objective is to assess the influence of root herbivore management (chemical pesticides and biological control) on roots, soil fauna (both root herbivores and non-target fauna), and soil carbon cycles. This field study focused on spatial and temporal variability in root herbivory within a single orchard-herbivore system and attempted to identify common influences of these fauna on plant growth and soilecosystem function. We are among a small number of labs world-wide employing the novel mini-rhizotron technique for the non-destructive study of root dynamics and carbon cycling in agricultural systems. The system is generally used in lighter soils, sandy-loams. The heavy clay soil in our experimental plots presented us with an opportunity to design tools and protocols uniquely suited to this soil type. Location The study site is a 1 acre experimental orchard in Davis, CA. Within this stand we have established a series of 2 m x 2.5 m sampling plots. These plots have been maintained free of herbaceous vegetation over the course of the study though a combination of hand weeding and/or flaming with a propane torch as necessary. The sampling plots are one meter from the bole of individual trees. Each sampling plot is divided into two 1 m x 2 m subplots separated by a 50 cm buffer. This buffer was established to minimize the effects of destructive sampling (i.e., soil collections, ion membrane installation) on measurements of soil respiration and root dynamics. The arrangement of these zones within a plot alternates between trees. Treatments Root herbivory treatments Spatial variability in root herbivory leads to difficulties in the assessment of root herbivore influences, because densities of root herbivores in individual plots can only be measured by conducting destructive harvests. To remedy this difficulty and reduce the effects of such spatial variability, we manipulated root herbivore densities on the 2 m x 2.5 m plots by adding locally-collected root herbivores to plots. Second- and third-instar Cyclocephala hirta larvae were collected from local habitats and added to field plots; we have collected several thousand individuals of this species from a golf course in Arbuckle, CA, a short distance from