Miracle-dz/UniFAR-FTUs huggingface dataset:
FebRNA: an automated fragment-ensemble-based model for building RNA 3D structures

Knowledge of RNA 3-dimensional (3D) structures is critical to understanding the important biological functions of RNAs. Although various structure prediction models have been developed, high accuracy of predicted RNA 3D structures is still limited to the RNAs with short length or with simple topology. In this work, we proposed a new model, namely FebRNA, for building RNA 3D structures through fragment assembly based on coarse-grained (CG) fragment ensembles. Specifically, FebRNA is composed of four processes: establishing the library of different types of CG fragment ensembles, building CG 3D structure ensemble through fragment assembly, identifying top-1 CG structure through a CG scoring function, and rebuilding the all-atom structure from the top-1 CG one. Extensive examination on different types of RNA structures indicates that FebRNA gives consistently reliable predictions on RNA 3D structures including pseudoknots, 3-way junction, 4-way and 5-way junctions, and RNAs in the RNA-Puzzles. FebRNA is available at website: https://github.com/Tan-group/FebRNA.
Episodic memory retrieval affects the onset and dynamics of evidence accumulation during value-based decisions

In neuroeconomics, there is much interest in understanding simple value-based choices where agents choose between visually presented goods, comparable to a shopping scenario in a supermarket. However, many everyday decisions are made in the physical absence of the considered goods, requiring agents to recall information about the goods from memory. Here, we asked whether and how this reliance on an internal memory representation affects the temporal dynamics of decision making on a cognitive and neural level. Participants performed a remember-and-decide task, in which they made simple purchasing decisions between money offers and snack items while undergoing EEG. Snack identity was presented either visually (value trials) or had to be recalled from memory (memory trials). Behavioral data indicated comparable choice consistency across both trial types, but considerably longer response times (RT) in memory trials. Drift-diffusion modeling suggested that this RT difference was due to longer non-decision time of decision processes as well as altered evidence accumulation dynamics (lower accumulation rate and higher decision threshold). The non-decision time effect was supported by a delayed onset of the lateralized readiness potential. These results show that both, decision and non-decision processes are prolonged when participants need to resort to internal memory representations during value-based decisions.
Spleen voltammetry assesses in real time norepinephrine release elicited by autonomic stimulation

Bioelectronic medicine uses neurostimulation devices to modulate the activity of autonomic nerves and restore function in visceral organs. The autonomic, noradrenergic, innervation of the spleen is implicated in the neural control of inflammation; for that reason, the spleen is the target of autonomic stimulation therapies tested in rheumatoid arthritis and other inflammatory diseases. However, there are no real time markers for successful engagement of the spleen by autonomic stimulation. Here, we use fast-scan cyclic voltammetry (FSCV) in the spleen to assess, in real time, the release of norepinephrine (NE) in response to autonomic stimulation in mice. We show that spleen voltammograms demonstrate oxidative current peaks at a voltage of ~0.8 V that is proportional up to a NE blood concentration of 30 to 300nM. The oxidative current increases within seconds in response to electrical splenic nerve stimulation and is blocked by interventions that deplete NE or inhibit NE release. Oxidative current increases in response to electrical vagus nerve stimulation (VNS) and is elicited by efferent, but not afferent, fiber-selective optogenetic VNS. Spleen cyclic voltammetry can potentially provide a real-time physiological marker for dose calibration and monitoring of the anti-inflammatory effectiveness of autonomic stimulation therapies targeting the spleen. neurotransmitter release in living tissue. We find that voltammetry in the spleen produces a signal that tracks in vivo concentration of NE and responds to electric and optogenetic autonomic stimulation. We also find that the amplitude of the stimulation-elicited voltammetry signal predicts the degree of suppression of TNF release in acute inflammation. Our findings indicate that voltammetry may be a feasible approach to assess in real time release of NE in the spleen during autonomic stimulation and potentially assist in the clinical programing of anti-inflammatory bioelectronic therapies.
Mechanisms regulating the frequency of inhibition-based gamma oscillations in primate prefrontal and parietal cortices

In primates, the dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices are critical nodes in the network mediating cognitive functions including attention and working memory. Notably, during working memory tasks, gamma oscillations, usually prominent in layer 3 (L3), are induced in both DLPFC and PPC but exhibit higher frequency in DLPFC. These oscillation frequency differences might be crucial for working memory function, but the mechanisms producing different oscillation frequencies in monkey DLPFC and PPC remain poorly understood. To investigate the basis of the DLPFC-PPC differences in oscillation frequency we studied GABAAR-mediated inhibition, which plays a crucial role in gamma oscillation production, in L3 pyramidal neurons (L3 PNs) from the rhesus monkey DLPFC or PPC. Recordings of GABAAR-mediated synaptic currents from L3 PNs, while suggesting a contribution to network synchronization in both areas, revealed no DLPFC-PPC differences in the strength or kinetics of GABAAR-mediated inhibition. Likewise, the expression of GABAAR genes in L3 PNs did not differ between regions. In the absence of differences in inhibition, DLPFC L3 PNs showed greater dendritic spine density and higher expression of AMPAR and NMDAR subunit genes relative to PPC L3 PNs, suggesting that the excitatory synaptic drive onto L3 PNs could be stronger in the DLPFC. Simulations in computational models of the cortical microcircuit showed that, with constant synaptic inhibition, increasing the strength of recurrent excitatory synaptic drive increased the network oscillation frequency. Hence, the DLPFC-PPC differences in gamma oscillation frequency could depend on stronger recurrent excitation in the DLPFC relative to PPC. Significance statement Gamma oscillations may contribute to the neural substrate of working memory and exhibit a higher frequency in the prefrontal (DLPFC) than parietal (PPC) areas of primate cortex. To investigate the basis of these oscillation frequency differences which may be crucial for working memory encoding, we studied GABAAR-mediated inhibition on L3 pyramidal neurons (L3 PNs) from rhesus monkey DLPFC or PPC. Our data revealed no DLPFC-PPC differences in GABAAR-mediated inhibition but showed greater dendritic spine density in DLPFC L3 PNs, suggesting stronger excitatory synaptic drive. Simulations in computational network models showed that stronger recurrent excitatory synaptic drive increased the network oscillation frequency, suggesting that the higher oscillation frequency could depend on stronger recurrent excitation in the DLPFC relative to PPC.
Genome report: chromosome-level draft assemblies of the snow leopard, African leopard, and tiger (Panthera uncia, Panthera pardus pardus, and Panthera tigris)

The big cats (genus Panthera) represent some of the most popular and charismatic species on the planet. Although some reference genomes are available for this clade, few are at the chromosome level, inhibiting high-resolution genomic studies. Here, we assemble genomes from three members of the genus, the tiger (Panthera tigris), the snow leopard (Panthera uncia), and the African leopard (Panthera pardus pardus), at chromosome or near-chromosome level. We used a combination of short- and long-read technologies, as well as proximity ligation data from Hi-C technology, to achieve high continuity and contiguity for each individual. We hope these genomes will aid in further evolutionary and conservation research of this iconic group of mammals.
A single-cell atlas of murine reproductive tissues during preterm labor

Preterm birth, the leading cause of perinatal morbidity and mortality worldwide, frequently results from the syndrome of preterm labor. Intra-amniotic infection is the best-established causal link to preterm labor, and involves premature activation of the parturition cascade in the reproductive tissues. Herein, we utilized single-cell RNA-sequencing (scRNA-seq) to generate a single-cell atlas of the murine uterus, decidua, and cervix in a model of infection-induced preterm labor. We show that preterm labor affects the transcriptomic profiles of specific immune and non-immune cell subsets. Shared and tissue-specific gene expression signatures were identified among affected cells. Importantly, determination of intercellular communications implicates specific cell types preterm labor-associated signaling pathways across tissues. Last, in silico comparison of murine and human uterine cell-cell interactions reveals conserved signaling pathways implicated in labor. Thus, scRNA-seq provides new insights into the preterm labor-driven cellular landscape and communications in the reproductive tissues.
Transcranial Direct Current Stimulation Alters the Waveform Shape of Cortical Gamma Oscillations

Neuronal oscillations in different frequency bands have been linked to a wide variety of cognitive functions, and may even be a fundamental mechanism of inter-regional communication. For this reason, manipulation of oscillatory activity via brain stimulation is a central goal in neuroscience research. However, the vast majority of studies characterise oscillatory activity solely in terms of amplitude and frequency. Oscillations can also be characterised by their waveform shape; the degree to which they resemble or deviate from sinusoids. Here we exploit Empirical Mode Decomposition (EMD), a novel method that allows quantification of oscillatory waveform shape. We show for the first time that transcranial direct current stimulation (tDCS) alters the waveform shape of gamma oscillatory activity in the visual cortex. Notably, changes in waveform shape were limited to one half of the phase cycle; anodal stimulation led to a relatively slower, and cathodal to a relatively faster, descending half-wave. tDCS is generally believed to affect cortical excitability via alteration of resting membrane potential. Interestingly, simulations of altered cortical excitability in a gamma-generating neuronal population indicated the waveform shape changes observed experimentally likely stem from stimulation of pyramidal neurons. These findings have implications for understanding the neural consequences of tDCS at the level of neuronal population phenomena such as cortical oscillations and underscore the importance of waveform shape as an important feature of neuronal oscillations.
Preterm infants voice processing is mediated by voice familiarity

Understanding how prematurity and language or voice familiarity impact on language perception at birth becomes crucial to determine which brain regions support language processing at this age, and how an atypical early sensory experience affects language-related brain areas. However, the time-frequency correlates of maternal voice processing remain to date unknown. Ten preterm and ten full-term newborns underwent EEG recordings during the presentation of their mother’s or a stranger’s speech. The speech could be naturalistic (presented in the forward order) or non-naturalistic (in the backward order). Time-frequency decomposition was performed and task-related responses were analyzed following a topographical data driven clustering using General Linear Mixed model approaches. Differential responses were observed in left and right temporal areas. In the left-temporal areas, a specific processing of the naturalistic mother compared to stranger speech was observed in low-frequency bands (theta and alpha bands), but taking antagonistic forms in the two groups i.e. a power increase for full-term and a power decrease (theta) or maintenance (alpha) in preterm babies. Left-temporal low-beta activity presents, in full-term babies, in the forward condition, a power increase for the maternal voice and a power decrease for the stranger voice, which were not observed in preterm babies. In the right-temporal scalp area, we observed in the low-beta and low-gamma bands a mother forward specific power-decrease in the preterm population specifically, with higher values for the mother backward, while terms were mostly activated by the most unfamiliar stimulus, the stranger backward voice.
An outstanding bacterial membranome requires CRISPR-Cas systems to avoid the intervention of phages

Antimicrobial resistance is widely recognized as a serious global public health problem. To combat this threat, a thorough understanding of bacterial genomes is necessary. The current wide availability of bacterial genomes provides us with an in-depth understanding of the great variability of dispensable genes and their relationship with antimicrobials. Some of these accessory genes are those involved in CRISPR-Cas systems, which are acquired immunity systems that are present in part of bacterial genomes. They prevent viral infections through small DNA fragments called spacers. But the vast majority of these spacers have not yet been associated with the virus they recognize, and this has been named CRISPR dark matter (spacers without associated recognized sequence). By analyzing the spacers of tens of thousands of genomes from six bacterial species highly resistant to antibiotics, we have been able to reduce the CRISPR dark matter from 80-90% to 15% in some cases. In addition, we have observed that, when a genome presents CRISPR-Cas systems, this is accompanied by particular collections of membrane proteins. Our results suggest that when a bacterium presents membrane proteins that make it compete better in its environment, and these proteins are in turn receptors for specific phages, it would be forced to acquire CRISPR-Cas immunity systems to avoid infection by these phages.
Neurofeedback training for improving motor performance in healthy adults: A systematic review and meta-analysis

Neurofeedback training (NFT) refers to a training where the participants voluntarily aim to manipulate their own brain activity using the sensory feedback abstracted from their brain activity. NFT has attracted attention in the field of motor learning for its potential to become an alternative or additional training method for general physical training. In this study, a systematic review of NFT studies for motor performance improvements in healthy adults and a meta-analysis on the effectiveness of NFT were conducted. To identify relevant studies published between January 1st, 1990 to August 3rd, 2021, a computerized search was performed using the databases, Web of Science, Scopus, PubMed, JDreamIII, and Ichushi-Web. Thirty-two studies were identified for the qualitative synthesis and 13 randomized controlled trials (286 subjects) for the meta-analysis. The meta-analysis revealed significant effects of NFT for motor performance improvement examined at the timing after the last NFT session (standardized mean difference = 0.96, 95% CI = 0.40–1.53), but with the existence of publication biases and substantial heterogeneity among the trials. Subsequent subgroup meta-analysis demonstrated reliable benefits when the NFT is performed longer than 1 week. The effectiveness of NFT for each motor performance measurement (e.g., speed, accuracy, and hand dexterity) remains unclear because of high heterogeneity or due to small sample size. Further accumulation of empirical NFT studies for motor performance improvement will be necessary to provide reliable evidence about the NFT effects on specific motor skills and to safely incorporate NFT into real-world scenarios.
Hydrothermal sulphur bacteria enhance mercury availability for coastal marine organisms

The hydrothermal compounds massively released into the sea by the geothermal power plant of Bouillante (Guadeloupe, Lesser Antilles) support the growth of sulphur-oxidising bacteria like around black smokers. Opportunistic animals of the bay were previously shown to actively seek and consume the bacterial biofilm. To investigate the role of these bacterial mats in enhancing the transfer of Hg, a highly toxic heavy metal, its concentrations were assessed in sediments, bacteria, and 6 low trophic levels animals from the Bouillante Bay and a Control Site nearby containing only natural sources of Hg. Concentrations of Hg in all samples from Bouillante were greater than those from the Control Site (2 to 627 times higher). A comparison with the Hg concentrations reported in the literature for similar samples types reveals that they are abnormally high in most Bouillante samples. Although bacterial biofilm contained high levels of Hg, the link between bacteria contribution to diet and Hg concentration was more complex than expected, which might be due to interspecific differences in Hg uptake and elimination rates. Species not consuming bacteria (i.e. filter feeders) still presented higher levels of Hg, suggesting that significant amounts of Hg are released along with discharge waters from the Bouillante geothermal plant, and are integrated through diffusion. Differences in Hg concentrations between tissues do not indicate that Hg contained in samples from animals was under the form of MeHg, lowering the biomagnification potential of Hg in the Bouillante Bay trophic food web. Overall, the Bouillante case study emphasises for the first time an important role played by sulphur bacteria mats as a vector of hydrothermal inorganic Hg, and potentially other trace metals emitted in vents area, through dietary pathways.
Title: Competition between severing and tubulin induced repair of microtubules

: Cytoskeletal structures aid in cell polarization, motility, and intracellular transport. Their functions are predicated on the rapid turnover of cytoskeleton proteins, which is achieved by the coordinated effort of multiple regulatory proteins whose dynamics is not well understood. Recent in-vitro experiments have investigated mixtures of regulatory proteins and cytoskeletal filaments and have reported novel synergistic effects. For example, free tubulin can repair nanoscale damages of microtubules created by proteins that sever microtubules and, in doing so, affect their disassembly. Based on this observation, we propose a model for microtubule severing as a competition between the processes of damage spreading and tubulin-induced repair. Using theory and simulations, we demonstrate that this model is in quantitative agreement with in vitro experiments. We predict the existence of a critical tubulin concentration above which severing becomes rare but fast. Additionally, we find that microtubule length control via severing with tubulin-induced repair is hypersensitive to changes in the concentration of free tubulin and leads to a dramatically increased dynamic range of filament lengths in steady state. Our work describes how the concerted action of multiple microtubule associated proteins produces novel dynamical properties of these cytoskeletal filaments. fast, and additionally, a dramatically increased dynamic range of microtubule filament lengths at steady state. This work describes how combining multiple microtubule associated proteins can produce novel dynamical properties which are not seen when these proteins are studied in isolation.
Evaluation of CA repeat arrays as targets for MeCP2 function in the brain

TheDNA bindingprotein MeCP2 isreportedto bindmethylated cytosine inCG andCAmotifs ingenomic 1 DNA, but it was recently proposed that arrays of tandemly repeated CA containing either methylated or 2 hydroxymethylated cytosine are the primary targets for MeCP2 binding and function. Here we investigated 3 the predictions of this hypothesis using a range of published datasets. We failed to detect enrichment of 4 cytosine modification at genomic CA repeat arrays in mouse brain regions and found no evidence for 5 preferential MeCP2 binding at CA repeats. Moreover, we did not observe a correlation between the CA 6 repeat density near genes and their degree of transcriptional deregulation when MeCP2 was absent. Our 7 results do not provide support for the hypothesis that CA repeats are key mediators of MeCP2 function. 8 Instead, we found that CA repeats are subject to CAC methylation to a degree that is typical of the 9 surrounding genome and contribute modestly to MeCP2-mediated modulation of gene expression in 10 accordance with their content of this canonical target motif.
Cortical magnification underlies differences across but not around the visual field

Human visual performance changes dramatically both across (eccentricity) and around (polar angle) the visual field. It is better at the fovea, decreases with eccentricity, and is better along the horizontal than vertical meridian and along the lower than the upper vertical meridian. However, all neurophysiological and virtually all behavioral studies of cortical magnification have investigated eccentricity effects without considering polar angle. Most performance differences due to eccentricity are eliminated when stimulus size is cortically magnified to equate the size of their cortical representation. But does cortical magnification underlie differences around the visual field? Here, the same human adult observers performed an orientation discrimination task with constant stimulus size at different locations as well as when stimulus size was magnified according to eccentricity and polar angle to equate their cortical representation. We found that although magnifying the stimulus eliminates differences across eccentricity, it does not do so around polar angle of the visual field. This finding indicates that limits in contrast sensitivity across eccentricity and around the visual field emerge from different anatomical and computational constraints. used to assess affected We report effect terms for and d for t-tests.
Retinotopic organization of feedback projections in primate early visual cortex: implications for active vision

Feedback connections play a major role in many theories of brain function. Previous studies of feedback connections to early visual areas have mainly concentrated on the representation of central visual fields. Here, injections of tracers at different eccentricities in areas V1 and V2 revealed retinotopically organized feedback. Peripheral injections revealed projections from 15 areas that are not labeled by central injections. Connection strengths for the majority of projections vary significantly with eccentricity in a systematic fashion with respect to distance and origin; whereas projections to central and upper visual fields are significantly stronger from ventral stream areas, peripheral and lower field projections are stronger from the dorsal stream. Non-invasive functional connectivity suggests a similar anatomical organization in humans. These features are discussed with respect to the cognitive and perceptual roles of these feedback pathways.