Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortical neuroprosthesis-mediated functional ipsilateral control of locomotion in rats with incomplete spinal cord injury

Control of voluntary limb movement is predominantly attributed to the contralateral motor cortex. However, increasing evidence suggests the involvement of ipsilateral cortical networks in this process, especially in motor tasks requiring bilateral coordination, such as locomotion. In this study, we combined a unilateral thoracic spinal cord injury (SCI) with a cortical neuroprosthetic approach to investigate the functional role of the ipsilateral motor cortex in rat movement. Our findings reveal that in all SCI rats, stimulation of the ipsilesional motor cortex promoted a bilateral synergy. This synergy involved the elevation of the contralateral foot along with ipsilateral hindlimb extension. Additionally, in two out of seven animals, stimulation of a sub-region of the hindlimb motor cortex modulated ipsilateral hindlimb flexion. Importantly, ipsilateral cortical stimulation delivered after SCI immediately alleviated multiple locomotor and postural deficits, and this effect persisted after ablation of the homologous motor cortex. These results provide strong evidence of a causal link between cortical activation and precise ipsilateral control of hindlimb movement. This study has significant implications for the development of future neuroprosthetic technology and our understanding of motor control in the context of spinal cord injury.
Trash-basket epiphytes as secondary foundation species: a review of their distribution and effects on biodiversity and ecosystem functions

Background Secondary foundation species (FS) are organisms that inhabit ecosystems structurally defined by a primary foundation species, providing additional structure to habitats and communities. Trash-basket epiphytes (TBE) are secondary FS that enhance arboreal soil accumulation, providing shelter to animals, and rooting sites for plants. While their importance may vary across biomes, TBE have been overlooked as drivers of biodiversity and ecosystem functions. Here, we discuss the prevalence of TBE across biomes, their effects on biodiversity and ecosystem functions, and future research directions. Methods We performed a systematic literature review of articles, books and theses and collated and synthesised information about the taxonomic distribution of TBE, their effects on ecosystem functions, and reports of plant-animal and plant-plant interactions. Then, we analysed the global distribution of TBE using a generalized linear model and summarised two studies to assess their effects on soil invertebrates. Results We identified 120 publications describing 209 species of TBE. Most TBE belong to Araceae (43%), Polypodiaceae (23%), and Orchidaceae (14%) and occur in all tropical and southern temperate forests. TBE richness peaks in the South-American Pacific mangroves, Eastern Cordillera Real, and the Napo moist forests. TBE effects on ecosystem functions include arboreal soil accumulation, water retention and temperature regulation in the canopy, and nutrient leaching through stem-flow. TBE provide shelter to species in more than 97 animal families, including from invertebrates to mammals, while 72 vascular plants have been reported to root in arboreal soil of TBE. Conclusions TBE are a compelling group of model organisms that can be used to study ecological processes such as facilitation cascades, niche construction, extended phenotypes, or the effects of secondary FS on biodiversity and ecosystem functioning. TBE should also be included in forest management plans to enhance the availability of microhabitats in the canopy supporting its associated flora and fauna.
An evolutionarily conserved odontode gene regulatory network underlies head armor formation in suckermouth armored catfish

Odontodes, i.e., teeth and tooth-like structures, consist of a pulp cavity and dentine covered by a mineralized cap. These structures first appeared on the outer surface of vertebrate ancestors and were repeatedly lost and gained across vertebrate clades; yet, the underlying genetic mechanisms and trajectories of this recurrent evolution remain long-standing mysteries. Here, we established suckermouth armored catfish (Ancistrus sp.; Loricariidae), which have uniquely evolved dermal odontodes (dermal denticles) all over most of their body surface, as an experimental model animal amenable to genetic manipulation for studying odontode development. Our histological analysis showed that suckermouth armored catfish develop dermal denticles through the previously defined odontode developmental stages. De novo transcriptomic profiling identified the conserved odontode genetic regulatory network (oGRN) as well as unique expression of paired like homeodomain 2 (pitx2), previously characterized as an early regulator of oGRN in teeth, in developing dermal denticles. Knockdown of pitx2 perturbed formation of the epithelial placode of dermal denticles and altered expression oGRN genes. By comprehensively identifying the genetic program for dermal odontode development in suckermouth armored catfish, this work illuminates how dermal odontodes independently evolved and diverged in distinct teleost lineages. Summary statement Cranial dermal denticles in suckermouth armored catfish develop via an evolutionarily conserved and unique odontode genetic regulatory network.
Two distinct networks containing position-tolerant representations of actions in the human brain

Humans can recognize other people’s actions in the social environment. This action recognition ability is rarely hindered by the movement of people in the environment. The neural basis of this tolerance to changes in the position of observed actions is not fully understood. Here, we aimed to identify brain regions capable of generalizing representations of actions across different positions and investigate the representational content of these regions. fMRI data were recorded from twenty-two subjects while they were watching video clips of ten different human actions in Point Light Display format. Each stimulus was presented in either the upper or the lower visual fields. Multivoxel pattern analysis and a searchlight technique were employed to identify brain regions that contain position-tolerant action representation: linear support vector machine classifiers were trained with fMRI patterns in response to stimuli presented in one position and tested with stimuli presented in another position. Results of this generalization test showed above-chance classification in the left and right lateral occipitotemporal cortex, right intraparietal sulcus, and right post-central gyrus. To explore the representational content of these regions, we constructed models based on the objective measures of movements and human subjective judgments about actions. We then evaluated the brain similarity matrix from the cross-position classification analysis based on these models. Results showed cross-position classifications in the lateral occipito-temporal ROIs were more strongly related to the subjective judgments, while those in the dorsal parietal ROIs were more strongly related to the objective movements. An ROI representational similarity analysis further confirmed the separation of the dorsal and lateral regions. These results provide evidence for two networks that contain abstract representations of human actions with distinct representational content.
X-DPI: A structure-aware multi-modal deep learning model for drug-protein interactions prediction

Motivation Identifying the drug-protein interactions (DPIs) is crucial in drug discovery, and a number of machine learning methods have been developed to predict DPIs. Existing methods usually use unrealistic datasets with hidden bias, which will limit the accuracy of virtual screening methods. Meanwhile, most DPIs prediction methods pay more attention to molecular representation but lack effective research on protein representation and high-level associations between different instances. To this end, we presented here a novel structure-aware multi-modal DPIs prediction model, X-DPI, performing on a curated industry-scale benchmark dataset. Results We built a high-quality benchmark dataset named GalaxyDB for DPIs prediction. This industry-scale dataset along with an unbiased training procedure resulted in a more robust benchmark study. For informative protein representation, we constructed a structure-aware graph neural network method from the protein sequence by combining predicted contact maps and graph neural networks. Through further integration of structure-based representation and high-level pre-trained embeddings for molecules and proteins, our model captured more effectively the feature representation of the interactions between them. As a result, X-DPI outperformed state-of-the-art DPIs prediction methods and obtained 5.30% Mean Square Error (MSE) improved in the DAVIS dataset and 8.89% area under the curve (AUC) improved in GalaxyDB dataset. Moreover, our model is an interpretable model with the transformer-based interaction mechanism, which can accurately reveal the binding sites between molecule and protein.
Dynamical differential covariance recovers directional network structure in multiscale neural systems

Investigating neural interactions is essential to understanding the neural basis of behavior. Many statistical methods have been used for analyzing neural activity, but estimating the direction of network interactions correctly and efficiently remains a difficult problem (1). Here, we derive dynamical differential covariance (DDC), a new method based on dynamical network models that detects directional interactions with low bias and high noise tolerance under nonstationarity conditions. The method was first validated and compared with other methods on networks with false positive motifs and multiscale neural simulations where the ground truth connectivity was known. When applied to recordings of resting-state functional magnetic resonance imaging (rs-fMRI) recordings, DDC consistently detected regional interactions with strong structural connectivity in over 1,000 individual subjects obtained by diffusion MRI (dMRI). DDC is a promising new family of methods for estimating functional connectivity that can be generalized to a wide range of dynamical models and recording techniques and to other applications where system identification from sparse data is needed. Significance Statement Through dynamical interactions with each other, neurons make it possible for us to sense, move and think. It is now possible to simultaneously record from many individual neurons and brain regions. Methods for analyzing these large-scale recordings are needed that can reveal how the patterns of activity give rise to behavior. We developed an efficient, intuitive and robust way to analyze these recordings and validated it on simulations of model neural networks where the ground truth was known. We called this method dynamical differential covariance (DDC) because it can estimate not only the presence of a connection but also which direction the information is flowing in a network between neurons or cortical areas. We also successfully applied DDC to brain imaging data from functional Magnetic Resonance Imaging.
Communication between the mediodorsal thalamus and prelimbic cortex regulates timing performance in rats

Predicting when future events will occur and adjusting behavior accordingly is critical to adaptive behavior. Despite this, little is known about the brain networks that encode time and how this ultimately impacts decision-making. One established finding is that the prefrontal cortex (PFC) and its non-human analogues (e.g., the rodent prelimbic cortex; PL) mediate timing. This provides a starting point for exploring the networks that support temporal processing by identifying areas that interact with the PFC during timing tasks. For example, substantial work has explored the role of frontostriatal circuits in timing. However, other areas are undoubtedly involved. The mediodorsal nucleus of the thalamus (MD) is an excellent candidate region. It shares dense, reciprocal connections with PFC-areas in both humans and non-human species and is implicated in cognition. However, causal data implicating MD-PFC interactions in cognition broadly is still sparse, and their role in timing specifically is currently unknown. To address this, we trained male rats on a time-based, decision-making task referred to as the ‘peak-inter- val’ procedure. During the task, presentation of a cue instructed the rats to respond after a specific interval of time elapsed (e.g., tone-8 seconds). We incorporated two cues; each requiring a response after a distinct time-interval (e.g., tone-8 seconds / light-16 seconds). We tested the effects of either reversibly inactivating the MD or PL individually or functionally disconnecting them on performance. All manipulations caused a comparable timing deficit. Specifically, responses showed little organization in time, as if primarily guided by motivational systems. These data expand our understanding of the networks that support timing and suggest that MD-PL interactions specifically are a core component. More broadly, our results suggest that timing tasks provide a reliable assay for characterizing the role of MD-PL interactions in cognition using rodents, which has been difficult to establish in the past.
High CXCL6 drives matrix expression and correlate with markers of poor outcome in IPF

Signaling via G protein-coupled receptors (GPCRs) can modulate levels of cyclic adenosine monophosphate (cAMP) and shape the functions of fibroblasts in idiopathic pulmonary fibrosis (IPF). We have identified Chemokine (C-X-C) Motif Ligand 6 (CXCL6) as a potential pro-fibrotic GPCR ligand. We tested the function of CXCL6 in ex vivo human donor and fibrotic lung fibroblasts and in an animal model of pulmonary fibrosis. We also measured levels of CXCL6 in the blood and bronchoalveolar lavage (BAL) of patients with IPF. CXCL6 decreased cAMP levels in a dose-dependent manner in Donor and IPF Fibroblasts. CXCL6 mRNA and protein were localized to epithelial cells. Administration of mCXCL5 (LIX, murine CXCL6 homologue) to mice increased collagen synthesis with and without bleomycin. CXCL6 increased Collagen I and α-SMA levels in Donor and IPF Fibroblasts. Silencing of CXCR1/2 as well as Reparixin, a CXCR1/2 inhibitor, blocked effects of CXCL6. Treprostinil blocked effects of CXCL6 only on levels of α-SMA but not on Collagen I. CXCL6 levels in the BAL of two separate cohorts of patients with IPF was associated with poor survival. We conclude that high CXCL6 drives fibroblast function and correlates with poor outcomes in IPF.
A gate and clamp regulate sequential DNA strand cleavage by CRISPR-Cas12a

CRISPR-Cas12a has been widely used for genome editing and diagnostic applications, yet it is not fully understood how RNA-guided DNA recognition activates the sequential cleavage of the non-target strand (NTS) followed by the target strand (TS). Here we used single-molecule magnetic tweezers microscopy, ensemble gel-based assays and nanopore sequencing to explore the coupling of DNA unwinding and cleavage. In addition to dynamic R-loop formation, we also directly observed transient dsDNA unwinding downstream of the 20 bp DNA:RNA hybrid and, following NTS cleavage and prior to TS cleavage, formation of a hyperstable “clamped” Cas12a-DNA intermediate resistant to DNA twisting. Alanine substitution of a conserved aromatic amino acid “gate” in the REC2 domain that normally caps the heteroduplex produced more frequent and extended downstream DNA breathing, a longer-lived twist-resistant state, and a 16-fold faster rate of TS cleavage. We suggest that both breathing and clamping events, regulated by the gate and by NTS cleavage, deliver the unwound TS to the RuvC nuclease and result from previously described REC2 and NUC domain motions.
FACT-mediated maintenance of chromatin integrity during transcription is essential for viability of mammalian stem cells

Replication and transcription machineries access DNA through unwrapping it from histone core. Preservation of nucleosome structure during replicatio n is a focus of intensive research, while maintenance of nucleosomes during transcription is less studied. Histone chaperone FACT is involved in transcription elongation, although whether it opens nucleosomes for polymerase or protects core histones from loss during passage of polymerase is still unclear. We used conditional knockout model of Ssrp1, subunit of FACT complex, to deplete FACT in mice and monitored consequences of FACT loss to establish the functional relevance of FACT in mammals. FACT loss was lethal for mice at all ages due to failure of hematopoietic and intestinal tissues. In these tissues, only the progenitors completely vanished upon FACT loss, while number of some other cell types were changed up and down. Using isolated stem cells of several tissues we showed that FACT loss was toxic only for stem cells, but not for cells which were differentiated in vitro. Chromatin accessibility in stem cells was increased genome wide upon FACT depletion in transcription dependentmanner. The most prominent response to the loss of chromatin integrity upon FACT depletion in cells was activation of interferon signaling, followed by accumulation of immune cells in sensitive organs. Thus, in undifferentiated mammalian cells FACT keeps chromatin stable during transcription elongation and this function of FACT is essential for viability of stem cells.
Humidity Reduces Rapid and Distant Airborne Dispersal of Viable Viral Particles in Classroom Settings

The transmission of airborne pathogens via aerosols is considered to be the main route through which a number of known and emerging respiratory diseases infect their hosts. It is therefore essential to quantify airborne transmission in closed spaces and determine the recommendations that should be implemented to minimize exposure to pathogens in built environments. We have developed a method to detect viable virus particles from aerosols by using an aerosolized bacteriophage Phi6 in combination with its host Pseudomonas phaseolicola, which when seeded on agar plates acts as a virus detector that can be placed at a range of distances away from an aerosol-generating source. Based on this method we present two striking results. (1) We consistently detected viable phage particles at distances of up to 18 feet away from the source within 15-minutes of exposure in a classroom equipped with a state of the art HVAC system. (2) Increasing the relative humidity beyond 40% significantly reduces dispersal. Our method can be used to quantify the exposure to pathogens at various distances from the source for different amounts of time, data which can be used to set safety standards for room capacity and to ascertain the efficacy of interventions that aim to reduce pathogen levels in closed spaces of specified sizes and intended uses. Summary We present a method to experimentally determine the exposure to airborne pathogens in closed spaces.
Improvement of association between confidence and accuracy after integration of discrete evidence over time

When making decisions in real-life, we may receive discrete pieces of evidence during a time period. Although subjects are able to integrate information from separate cues to improve their accuracy, confidence formation is controversial. Due to a strong positive relation between accuracy and confidence, we predicted that confidence followed the same characteristics as accuracy and would improve following the integration of information collected from separate cues. We applied a Random-dot-motion discrimination task in which participants had to indicate the predominant direction of dot motions by saccadic eye movement after receiving one or two brief stimuli (i.e., pulse(s)). The interval of two pulses (up to 1s) was selected randomly. Color-coded targets facilitated indicating confidence simultaneously. Using behavioral data, computational models, pupillometry and EEG methodology we show that in double-pulse trials: (i) participants improve their confidence resolution rather than reporting higher confidence comparing with single-pulse trials, (ii) the observed confidence follow neural and pupillometry markers of confidence, unlike in weak and brief single-pulse trials. Overall, our study showed improvement of associations between confidence and accuracy in decisions resulted from the integration of evidence separated by different temporal gaps.
Linking plant growth promoting arbuscular mycorrhizal colonization with bacterial plant sulfur supply

Sulfur (S) exists in organically bound complexes (∼95%), predominantly as sulfonates, and are not directly plant available. Specific soil bacteria can mobilise sulfonates but very little is known about these bacteria in the hyphosphere. Since mycorrhizal fungi support growth of the majority of land plants, hyphosphere desulfonating bacteria may be of substantial benefit to the plant host. This study analysed the effect of AM inoculation with Rhizophagus irregularis (former G. intraradices, Glomus) and a mix of six AM species (Mixed) on PGP, microbial communities and sulfonate mobilising bacteria with L. perenne, Agrostis stolonifera and Plantago lanceolata as plant hosts in bi-compartmental microcosms and A. stolonifera in PGP pot experiments. AM inoculation significantly increased plant growth, percentage root colonisation and the quantity of cultivable desulfonating bacteria in the hyphosphere over pre-inoculated soil for all plants. Community analysis via PCR-DGGE revealed significantly different bacterial and fungal communities post inoculation. Analysis of the sulfonate mobilising asfA gene revealed a significantly altered community and novel bacterial isolates with this important functional ability post-inoculation. The results demonstrate that AM inoculation increased plant biomass yield, AM root colonisation and altered bacterial and fungal community dynamics in the hyphosphere. AM inoculated microcosms had an increased abundance of desulfonating bacteria that may be beneficial for plant-S supply. Research highlights Inoculation with AM fungi was shown to promote plant growth and harbour larger populations of sulfonate mobilising bacteria. Post-inoculation hyphospheric bacterial and saprotrophic fungal communities were shown to differ significantly in composition and abundance. Analysis of sulfonate mobilising bacteria revealed novel presumptive species in possession of the asfA gene associated with AM hyphae. AM inoculation was shown to significantly impact the asfA positive bacterial community composition.
Single-cell Chromatin Accessibility and Lipid Profiling Reveals a Metabolic Shift in Adipocytes Induced by Bariatric Surgery

Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy homeostasis and utilization, we hypothesized that VSG exerts its influences, in part, by modulating adipose functional states. We applied single-cell ATAC sequencing and lipid profiling to inguinal and epididymal adipose depots from mice that received sham surgery or VSG. We observed depot-specific cellular composition and chromatin accessibility patterns that were altered by VSG. Specifically, accessibility at Scd1, a fatty acid desaturase, was substantially reduced after VSG in mature adipocytes of inguinal but not epididymal depots. This was accompanied by reduced accumulation of SCD1-produced unsaturated fatty acids. Given these findings and reports that reductions in Scd1 attenuate obesity and insulin resistance and that unsaturated fatty acids stimulate glucose uptake, storage, and oxidation, our results suggest VSG exerts its beneficial effects through modifications of fatty acid profiles mediated by Scd1.