Miracle-dz/UniFAR-FTUs huggingface dataset:
Lacking social support is associated with structural divergences in hippocampus–default network co-variation patterns

Elaborate social interaction is a pivotal asset of the human species. The complexity of people’s social lives may constitute the dominating factor in the vibrancy of many individuals’ environment. The neural substrates linked to social cognition thus appear especially susceptible when people endure periods of social isolation: here, we zoom in on the systematic inter-relationships between two such neural substrates, the allocortical hippocampus (HC) and the neocortical default network (DN). Previous human social neuroscience studies have focused on the DN, while HC subfields have been studied in most detail in rodents and monkeys. To bring into contact these two separate research streams, we directly quantified how DN subregions are coherently co-expressed with specific HC subfields in the context of social isolation. A two-pronged decomposition of structural brain scans from ∼40,000 UK Biobank participants linked lack of social support to mostly lateral subregions in the DN patterns. This lateral DN association co-occurred with HC patterns that implicated especially subiculum, presubiculum, CA2, CA3, and dentate gyrus. Overall, the subregion divergences within spatially overlapping signatures of HC-DN co-variation followed a clear segregation divide into the left and right brain hemispheres. Separable regimes of structural HC-DN co-variation also showed distinct associations with the genetic predisposition for lacking social support at the population level.
Improved radiation expression profiling in blood by sequential application of sensitive and specific gene signatures

Purpose Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap some viral infections. We recently showed that these human radiation signatures produced unexpected false positive misclassification of Influenza and Dengue infected samples. The present study investigates these and other confounders, and then mitigates their effects on signature accuracy. Methods This study investigated recall by previous and novel radiation signatures independently derived from multiple Gene Expression Omnibus datasets on common and rare non-malignant blood disorders and blood-borne infections (thromboembolism, S. aureus bacteremia, malaria, sickle cell disease, polycythemia vera, and aplastic anemia). Normalized expression levels of signature genes are used as input to machine learning-based classifiers to predict radiation exposure in other hematological conditions. Results Except for aplastic anemia, these blood-borne disorders modify the normal baseline expression values of genes present in radiation signatures, leading to false-positive misclassification of radiation exposures in 8 to 54% of individuals. Shared changes, predominantly in DNA damage response and apoptosis-related gene transcripts in radiation and confounding hematological conditions, compromise the utility of these signatures for radiation assessment. These confounding conditions (sickle cell disease, thromboembolism, S. aureus bacteremia, malaria) induce neutrophil extracellular traps, initiated by chromatin decondensation, DNA damage response and fragmentation followed by programmed cell death. Riboviral infections (for example, Influenza, Dengue fever) are proposed to deplete RNA binding proteins, inducing R-loops in chromatin which collide with replication forks resulting in DNA damage, and apoptosis. To mitigate the effects of confounders, we evaluated predicted radiation positive samples with novel gene expression signatures derived from radiation-responsive transcripts encoding secreted blood plasma proteins whose expression levels are unperturbed by these conditions. Conclusions This approach identifies and eliminates misclassified samples with underlying hematological or infectious conditions, leaving only samples with true radiation exposures. Diagnostic accuracy is significantly improved by selecting genes that maximize both sensitivity and specificity in the appropriate tissue using combinations of the best signatures for each of these classes of signatures.
Perinatal Inflammation Disturbs Secondary Germinal Zone Neurogenesis and Gliogenesis Producing Deficits in Sociability

Epidemiologic studies have demonstrated that infections during pregnancy increase the risk of offspring developing Schizophrenia, Autism, Depression and Bipolar Disorder and have implicated interleukin-6 (IL-6) as a causal agent. However, other cytokines have been associated with psychiatric disorders; therefore, it remains to be established whether elevating IL-6 is sufficient to alter the trajectory of neural development. Furthermore, most rodent studies have manipulated the maternal immune system at mid-gestation, which affects the stem cells and progenitors in both the primary and secondary germinal matrices. Therefore, a question that remains to be addressed is whether elevating IL-6 when the secondary germinal matrices are most active will affect brain development. Here, we have increased IL-6 from postnatal days 3-6, when the secondary germinal matrices are rapidly expanding. Using Nestin-CreERT2 fate mapping we show that this transient increase in IL-6 decreased neurogenesis in the dentate gyrus of the dorsal hippocampus, reduced astrogliogenesis in the prefrontal cortex and amygdala and decreased oligodendrogenesis in the body and splenium of the corpus callosum all by ∼50%. Moreover, the IL-6 treatment elicited behavioral changes classically associated with neurodevelopmental disorders. As adults, IL-6 injected male mice lost social preference in the social approach test, spent ∼30% less time socially engaging with sexually receptive females and produced ∼50% fewer ultrasonic vocalizations during mating. They also engaged ∼50% more time in self-grooming behavior and had an increase in inhibitory avoidance. Altogether, these data provide new insights into the biological mechanisms linking perinatal immune activation to complex neurodevelopmental brain disorders. Significance statement In these studies, we doubled circulating IL-6 levels in mice from postnatal days 3-6 to test the hypothesis that this would be sufficient to disturb neural development. More specifically, we hypothesized that IL-6 would affect postnatal neural stem cell and progenitor expansion and specification. We show that this transient increase in IL-6 decreases the numbers of granule neurons in the dorsal hippocampus, astrocytes in the prefrontal cortex and amygdala and oligodendrocytes in the corpus callosum. Importantly, this transient increase in IL-6 changes the sociability, communication and repetitive behaviors of the treated mice as adults, which are core symptoms pertinent to several neurodevelopmental psychiatric disorders.
High-throughput phenotyping of leaf discs infected with grapevine downy mildew using shallow convolutional neural networks

Objective and standardized recording of disease severity in mapping crosses and breeding lines is a crucial step in characterizing resistance traits utilized in breeding programs and to conduct QTL or GWAS studies. Here we report a system for automated high-throughput scoring of disease severity on inoculated leaf discs. As proof of concept, we used leaf discs inoculated with Plasmopara viticola causing grapevine downy mildew (DM). This oomycete is one of the major grapevine pathogens and has the potential to reduce grape yield dramatically if environmental conditions are favorable. Breeding of DM resistant grapevine cultivars is an approach for a novel and more sustainable viticulture. This involves the evaluation of several thousand inoculated leaf discs from mapping crosses and breeding lines every year. Therefore, we trained a shallow convolutional neural-network (SCNN) for efficient detection of leaf disc segments showing P. viticola sporangiophores. We could illustrate a high and significant correlation with manually scored disease severity used as ground truth data for evaluation of the SCNN performance. Combined with an automated imaging system, this leaf disc-scoring pipeline has the potential to reduce the amount of time during leaf disc phenotyping considerably. The pipeline with all necessary documentation for adaptation to other pathogens is freely available.
Deep learning-based algorithm for predicting the live birth potential of mouse embryos

In assisted reproductive technology (ART), embryos produced by in vitro fertilization (IVF) are graded according to their live birth potential, and high-grade embryos are preferentially transplanted. However, the rate of live birth following clinical ART remains low worldwide, suggesting that grading is inaccurate. One explanation is that grading is classically based on the characteristic shape of embryos at a limited number of developmental stages and does not consider the shape of embryos and intracellular structures, e.g., nuclei, at various stages important for normal embryogenesis. Therefore, here we developed a Normalized Multi-View Attention Network (NVAN) that directly predicts live birth potential from nuclear structural features in live-cell fluorescence images taken of mouse embryos across a wide range of stages. The classification accuracy of our method was 83.87%, which greatly exceeded that of existing machine-learning methods and that of visual inspection by embryo culture specialists. By visualizing the features that contributed most to the prediction of live birth potential, we found that the size and shape of the cell nucleus at the morula stage and at the time of cell division were important for live birth prediction. We anticipate that our method will help ART and developmental engineering as a new basic technology for IVF embryo selection.
Corticostriatal Suppression of Appetitive Pavlovian Conditioned Responding

The capacity to suppress learned responses is essential for animals to adapt in dynamic environments. Extinction is a process by which animals learn to suppress conditioned responding when an expected outcome is omitted. The infralimbic (IL) cortex to nucleus accumbens shell (NAcS) neural circuit is implicated in suppressing conditioned responding after extinction, especially in the context of operant cocaine-seeking behavior. However, the role of the IL-to-NAcS neural circuit in the extinction of responding to appetitive Pavlovian cues is unknown, and the psychological mechanisms involved in response suppression following extinction are unclear. We trained male Long Evans rats to associate a 10 s auditory conditioned stimulus (CS; 14 trials per session) with a sucrose unconditioned stimulus (US; 0.2 ml per CS) in a specific context, and then following extinction in a different context, precipitated a renewal of CS responding by presenting the CS alone in the original Pavlovian conditioning context. Unilateral, optogenetic stimulation of the IL-to-NAcS circuit selectively during CS trials suppressed renewal. In a separate experiment, IL-to-NAcS stimulation suppressed CS responding regardless of prior extinction and impaired extinction retrieval. Finally, IL-to-NAcS stimulation during the CS did not suppress the acquisition of Pavlovian conditioning but was required for the subsequent expression of CS responding. These results are consistent with multiple studies showing that the IL-to-NAcS neural circuit is involved in the suppression of operant cocaine-seeking, extending these findings to appetitive Pavlovian cues. The suppression of appetitive Pavlovian responding following IL-to-NAcS circuit stimulation, however, does not appear to be an extinction-dependent process. SIGNIFICANCE STATEMENT Extinction is a form of inhibitory learning through which animals learn to suppress conditioned responding in the face of nonreinforcement. We investigated the role of the IL cortex inputs to the NAcS in the extinction of responding to appetitive Pavlovian cues and the psychological mechanisms involved in response suppression following extinction. Using in vivo optogenetics, we found that stimulating the IL-to-NAcS neural circuit suppressed context-induced renewal of conditioned responding after extinction. In a separate experiment, stimulating the IL-to-NAcS circuit suppressed conditioned responding in an extinction-independent manner. These findings can be used by future research aimed at understanding how corticostriatal circuits contribute to behavioral flexibility and mental disorders that involve the suppression of learned behaviors.
Isolation, ‘omics characterization and organotypic culture of alveolar type II pulmonary epithelial cells

The alveolar type II (AT2) epithelial cell fraction includes the stem cells of the pulmonary alveoli, functioning in lung homeostasis and post-injury repair. AT2 cells have been characterized primarily in situ, in transgenic mouse models. We report a new methodology for their isolation, their “omics” characterization and stroma-cell-free organotypic culture. Our multi-omics analysis identified high expression of genes involved in oxidative phosphorylation and of AP-1 components, as well as new phosphorylation sites in AT2 biomarkers. Furthermore, we show that supplementation with KGF, FGF10 & HGF suffices for the in vitro proliferation of AT2 cells and formation of alveolar organoids, suggesting that AT2-based organotypic development depends on ligands of the c-Met and FGFR2 receptors. The reported methodology and in-depth molecular characterization provide new tools for the in vitro and in vivo functional analysis of pulmonary cells and of mouse models of lung disease.
Trait empathy modulates music-related functional connectivity

It has been well established through behavioural studies that empathy significantly influences music perception. Such individual differences typically manifest as variability in whole brain functional connectivity patterns. To date, nobody has examined the modulatory effect of empathy on functional connectivity patterns during continuous music listening. In the present study, we seek to investigate the global and local connectivity patterns of 36 participants whose fMRI scanning was done by employing the naturalistic paradigm wherein they listened to a continuous piece of music. We used graph-based measures of functional connectivity to identify how cognitive and affective components of empathy modulate functional connectivity. Partial correlation between Eigenvector centrality and measures of empathy showed that cognitive empathy is associated with higher centrality in the sensorimotor regions responsible for motor mimicry while affective empathy showed higher centrality in regions related to auditory affect processing. We furthermore identified a left-hemispheric dominance in the modulatory effect of affective empathy particularly in the Orbitofrontal cortex and the temporal pole. Results are discussed in relation to various theoretical models of empathy and music cognition.
White matter microstructure shows sex differences in late childhood: Evidence from 6,797 children

Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging (dMRI) approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here we rigorously characterized sex differences in white matter microstructure among over 6,000 children from the Adolescent Brain Cognitive Development (ABCD) Study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model - diffusion tensor imaging (DTI) - and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.
IRE1/XBP1 signaling promotes skeletal muscle regeneration through a cell non-autonomous mechanism

Skeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways activated in both injured myofibers and satellite cells. The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in ER. However, the role of individual arms of the UPR in skeletal muscle regeneration remain less understood. In the present study, we demonstrate that IRE1α-XBP1 pathway is activated in skeletal muscle of mice upon injury. Myofiber-specific deletion of IRE1 or XBP1 in mice diminishes skeletal muscle regeneration accompanied with reduced number of satellite cells and their fusion to injured myofibers. Ex vivo cultures of myofiber explants demonstrate that ablation of IRE1α reduces the proliferative capacity of myofiber-associated satellite cells. Myofiber-specific deletion of IRE1α dampens Notch signaling and canonical NF-κB pathway in skeletal muscle of mice. Our results also demonstrate that targeted ablation of IRE1α reduces skeletal muscle regeneration in the mdx model of Duchenne muscular dystrophy. Collectively, our results reveal that the IRE1α-mediated signaling promotes muscle regeneration through augmenting the proliferation of satellite cells in a cell non-autonomous manner.
Efficacy of a Novel Exoskeletal Robot for Locomotor Rehabilitation in Stroke Patients: A Multi-center, Non-inferiority, Randomized Controlled Trial

Objective: To investigate the efficacy and safety of a novel lower-limb exoskeletal robot, BEAR-H1 (Shenzhen Milebot Robot Technology), in the locomotor function of subacute stroke patients. Methods: The present study was approved by the ethical committee of the First Affiliated Hospital of Nanjing Medical University (No. 2019-MD-43), and registration was recorded on the Chinese Clinical Trial Registry with a unique identifier: ChiCTR2100044475. A total of 130 patients within 6 months of stroke were randomly divided into two groups: the robot group and the control group. The control group received routine training for walking, while in the robot group, BEAR-H1 lower-limb exoskeletal robot was used for locomotor training. Both groups received two sessions daily, 5 days a week for 4 weeks consecutively. Each session lasted 30 min. Before treatment, after treatment for 2 weeks, and 4 weeks, the patients were assessed based on the 6-minute walking test (6MWT), functional ambulation scale (FAC), Fugl-Meyer assessment lower-limb subscale (FMA-LE), and Vicon gait analysis. Results: After a 4-week intervention, the results of 6MWT, FMA-LE, FAC, cadence, and gait cycle in the two groups significantly improved (P < 0.05), but there was no significant difference between the two groups (P > 0.05). The ratio of stance phase to that of swing phase, swing phase symmetry ratio (SPSR), and step length symmetry ratio (SLSR) was not significantly improved after 4 weeks of training in both the groups. Further analyses revealed that the robot group exhibited potential benefits, as the point estimates of 6MWT and Δ6MWT (post-pre) at 4 weeks were higher than those in the control group. Additionally, within-group comparison showed that patients in the robot group had a significant improvement in 6MWT earlier than their counterparts in the control group. Conclusions: The rehabilitation robot in this study could improve the locomotor function of stroke patients; however, its effect was no better than conventional locomotor training.
Metabolomics of healthy and stony coral tissue loss disease affected Montastraea cavernosa corals

Stony coral tissue loss disease, first observed in Florida in 2014, has now spread along the entire Florida Reef Tract and on reefs in many Caribbean countries. The disease affects a variety of coral species with differential outcomes, and in many instances results in whole-colony mortality. We employed untargeted metabolomic profiling of Montastraea cavernosa corals affected by stony coral tissue loss disease to identify metabolic markers of disease. Herein, extracts from apparently healthy, diseased, and recovered corals, Montastraea cavernosa, collected at a reef site near Ft. Lauderdale, Florida were subjected to liquid-chromatography mass spectrometry-based metabolomics. Unsupervised principal component analysis reveals wide variation in metabolomic profiles of healthy corals of the same species, which differ from diseased corals. Using a combination of supervised and unsupervised data analyses tools, we describe metabolite features that explain variation between the apparently healthy corals, between diseased corals, and between the healthy and the diseased corals. By employing a culture-based approach, we assign sources of a subset of these molecules to the endosymbiotic dinoflagellates, Symbiodiniaceae. Specifically, we identify various endosymbiont-specific lipid classes, such as betaine lipids, glycolipids, and tocopherols, which differentiate samples taken from apparently healthy corals and diseased corals. Given the variation observed in metabolite fingerprints of corals, our data suggests that metabolomics is a viable approach to link metabolite profiles of different coral species with their susceptibility and resilience to numerous coral diseases spreading through reefs worldwide.
Loneliness is linked to specific subregional alterations in hippocampus-default network covariation

Social interaction complexity makes humans unique. But in times of social deprivation this strength risks to expose important vulnerabilities. Human social neuroscience studies have placed a premium on the default network (DN). In contrast, hippocampus (HC) subfields have been intensely studied in rodents and monkeys. To bridge these two literatures, we here quantified how DN subregions systematically co-vary with specific HC subfields in the context of subjective social isolation (i.e., loneliness). By co-decomposition using structural brain scans of ∼40,000 UK Biobank participants, loneliness was specially linked to midline subregions in the uncovered DN patterns. These association cortex signatures coincided with concomitant HC patterns implicating especially CA1 and molecular layer. These patterns also showed a strong affiliation with the fornix white-matter tract and the nucleus accumbens. In addition, separable signatures of structural HC-DN co-variation had distinct associations with the genetic predisposition for loneliness at the population level.