Miracle-dz/UniFAR-FTUs huggingface dataset:
Does the phase of ongoing EEG oscillations predict auditory perception?

Effective processing of information from the environment requires the brain to selectively sample relevant inputs. The visual perceptual system has been shown to sample information rhythmically, oscillating rapidly between more and less input-favorable states. Evidence of parallel effects in auditory perception is inconclusive. Here, we combined a bilateral pitch-identification task with electroencephalography (EEG) to investigate whether the phase of ongoing EEG predicts auditory discrimination accuracy. We compared prestimulus phase distributions between correct and incorrect trials. Shortly before stimulus onset, each of these distributions showed significant phase concentration, but centered at different phase angles. The effects were strongest in theta and beta frequency bands. The divergence between phase distributions showed a linear relation with accuracy, accounting for at least 10% of inter-individual variance. Discrimination performance oscillated rhythmically at a rate predicted by the neural data. These findings indicate that auditory discrimination threshold oscillates over time along with the phase of ongoing EEG activity. Thus, it appears that auditory perception is discrete rather than continuous, with the phase of ongoing EEG oscillations shaping auditory perception by providing a temporal reference frame for information processing.
Untangling the Animacy Organization of Occipitotemporal Cortex

Some of the most impressive functional specializations in the human brain are found in the occipitotemporal cortex (OTC), where several areas exhibit selectivity for a small number of visual categories, such as faces and bodies, and spatially cluster based on stimulus animacy. Previous studies suggest this animacy organization reflects the representation of an intuitive taxonomic hierarchy, distinct from the presence of face- and body-selective areas in OTC. Using human functional magnetic resonance imaging, we investigated the independent contribution of these two factors—the face-body division and taxonomic hierarchy—in accounting for the animacy organization of OTC and whether they might also be reflected in the architecture of several deep neural networks that have not been explicitly trained to differentiate taxonomic relations. We found that graded visual selectivity, based on animal resemblance to human faces and bodies, masquerades as an apparent animacy continuum, which suggests that taxonomy is not a separate factor underlying the organization of the ventral visual pathway. SIGNIFICANCE STATEMENT Portions of the visual cortex are specialized to determine whether types of objects are animate in the sense of being capable of self-movement. Two factors have been proposed as accounting for this animacy organization: representations of faces and bodies and an intuitive taxonomic continuum of humans and animals. We performed an experiment to assess the independent contribution of both of these factors. We found that graded visual representations, based on animal resemblance to human faces and bodies, masquerade as an apparent animacy continuum, suggesting that taxonomy is not a separate factor underlying the organization of areas in the visual cortex.
Linking scales of life-history variation with population structure in Atlantic cod

It is increasing recognised that sustainable exploitation of marine fish requires the consideration of population diversity and associated productivity. This study used a combination of genotypic screening and phenotypic traits to define the scale of population structuring in Atlantic cod inhabiting the northern North Sea (ICES 4a) and Scottish west coast (6a). The genetic analysis indicated an isolation by distance pattern with an even finer scale structuring than previously reported, that persisted over a decade and between feeding and spawning seasons. Spatial variation in phenotypic traits reflected genetic variation with cod maturing later and at a larger size near the Viking Bank in 4a. The identified population structuring provides an explanation for differences in historic changes in maturation schedules and the temperature exposure recorded in previous electronic tagging studies. The study also highlights how the mismatch between stock divisions and population units is leading to a misunderstanding about stock recovery.
Asymmetric robustness in the feedback control of the retinoic acid network response to environmental disturbances

Retinoic acid (RA) is a developmental signal whose perturbation is teratogenic. We show that early embryos exhibit effective RA signaling robustness to physiological, non-teratogenic, disturbances of this pathway. Transcriptomic analysis of transient physiological RA manipulations during embryogenesis supported the robustness of RA signaling by identifying mainly changes consistent with the progression of embryogenesis and not dramatic treatment-induced changes. Transcriptomic pattern comparisons revealed that RA manipulation led to a network-wide feedback regulation aimed at achieving signaling robustness and normalizing RA levels. A trajectory analysis of target gene and RA network responses identified an asymmetric robustness with a high sensitivity to reduced RA levels, and an activation threshold to increased levels. Furthemore, high robustness to increased RA inversely correlated with a low response to reduced RA. Biological replicates with similar robustness levels mounted responses whose composition likely varies based on genetic polymorphisms to achieve similar outcomes providing insights on the robustness mechanisms.
Intrauterine growth restriction causes cellular, molecular, and behavioral deficits consistent with abnormal dentate gyrus neurogenesis in mice

Background Children born with intrauterine growth restriction (IUGR) are at increased risk for cognitive impairment including learning and memory deficits. Dentate gyrus (DG) granule neurons relay cortical information into the hippocampus proper for memory formation, and their production is highly dependent on environmental signals. However, it is unknown whether IUGR affects DG neurogenesis, and thus provides a potential mechanism underlying abnormal learning and memory function. Methods Using a hypertensive disease of pregnancy mouse model of IUGR, we assessed multiple behaviors, quantified neural stem and progenitor cells (NSPCs) and developing neurons in the DG, and characterized transcriptional effects on molecular pathways in the hippocampus. Results We found that the predominant behavioral phenotype in IUGR offspring, short-term implicit learning and memory deficits, was associated with accelerated DG neurogenesis and NSPC depletion. Consistent with known molecular regulators of DG neurogenesis, we also found strong evidence for decreased Wnt pathway activity following IUGR. Conclusion We have discovered that postnatal memory deficits are associated with accelerated NSPC differentiation following IUGR, a phenotype that could be explained by decreased Wnt signaling.
Redefining the Clostridioides difficile σB Regulon: σB Activates Genes Involved in Detoxifying Radicals That Can Result from the Exposure to Antimicrobials and Hydrogen Peroxide

Sigma B is the alternative sigma factor governing stress response in many Gram-positive bacteria. In C. difficile, a sigB mutant shows pleiotropic transcriptional effects. Here, we determine genes that are likely direct targets of σB by evaluating the transcriptional effects of σB overproduction, provide biochemical evidence of direct transcriptional activation by σB, and show that σB-dependent genes can be activated by antimicrobials. Together, our data suggest that σB is a key player in dealing with toxic radicals. ABSTRACT In many Gram-positive bacteria, the general stress response is regulated at the transcriptional level by the alternative sigma factor sigma B (σB). In C. difficile, σB has been implicated in protection against stressors such as reactive oxygen species (ROS) and antimicrobial compounds. Here, we used an anti-σB antibody to demonstrate time-limited overproduction of σB in C. difficile despite its toxicity at higher cellular concentrations. This toxicity eventually led to the loss of the plasmid used for anhydrotetracycline-induced σB gene expression. Inducible σB overproduction uncouples σB expression from its native regulatory network and allows for the refinement of the previously proposed σB regulon. At least 32% of the regulon was found to consist of genes involved in the response to reactive radicals. Direct gene activation by C. difficile σB was demonstrated through in vitro runoff transcription of specific target genes (cd0350, cd3614, cd3605, and cd2963). Finally, we demonstrated that different antimicrobials and hydrogen peroxide induce these genes in a manner dependent on this sigma factor, using a plate-based luciferase reporter assay. Together, our work suggests that lethal exposure to antimicrobials may result in the formation of toxic radicals that lead to σB-dependent gene activation. IMPORTANCE Sigma B is the alternative sigma factor governing stress response in many Gram-positive bacteria. In C. difficile, a sigB mutant shows pleiotropic transcriptional effects. Here, we determine genes that are likely direct targets of σB by evaluating the transcriptional effects of σB overproduction, provide biochemical evidence of direct transcriptional activation by σB, and show that σB-dependent genes can be activated by antimicrobials. Together, our data suggest that σB is a key player in dealing with toxic radicals.
Microscopic Chromosomal Structural and Dynamical Origin of Cell Differentiation and Reprogramming

As an essential and fundamental process of life, cell development involves large-scale reorganization of the three-dimensional genome architecture, which forms the basis of gene regulation. Here, we develop a landscape-switching model to explore the microscopic chromosomal structural origin of the embryonic stem cell (ESC) differentiation and the somatic cell reprogramming. We show that chromosome structure exhibits significant compartment-switching in the unit of topologically associating domain. We find that the chromosome during differentiation undergoes monotonic compaction with spatial re-positioning of active and inactive chromosomal loci towards the chromosome surface and interior, respectively. In contrast, an over-expanded chromosome, which exhibits universal localization of loci at the chromosomal surface with erasing the structural characteristics formed in the somatic cells, is observed during reprogramming. We suggest an early distinct differentiation pathway from the ESC to the terminally differentiated cell, giving rise to early bifurcation on the Waddington landscape for the ESC differentiation. Our theoretical model including the non-equilibrium effects, draws a picture of the highly irreversible cell differentiation and reprogramming processes, in line with the experiments. The predictions from our model provide a physical understanding of cell differentiation and reprogramming from the chromosomal structural and dynamical perspective and can be tested by future experiments.
RNA-Seq Analysis Reveals Localization-Associated Alternative Splicing across 13 Cell Lines

Alternative splicing, a ubiquitous phenomenon in eukaryotes, is a regulatory mechanism for the biological diversity of individual genes. Most studies have focused on the effects of alternative splicing for protein synthesis. However, the transcriptome-wide influence of alternative splicing on RNA subcellular localization has rarely been studied. By analyzing RNA-seq data obtained from subcellular fractions across 13 human cell lines, we identified 8720 switching genes between the cytoplasm and the nucleus. Consistent with previous reports, intron retention was observed to be enriched in the nuclear transcript variants. Interestingly, we found that short and structurally stable introns were positively correlated with nuclear localization. Motif analysis reveals that fourteen RNA-binding protein (RBPs) are prone to be preferentially bound with such introns. To our knowledge, this is the first transcriptome-wide study to analyze and evaluate the effect of alternative splicing on RNA subcellular localization. Our findings reveal that alternative splicing plays a promising role in regulating RNA subcellular localization.
Towards More Reliable Unsupervised Tissue Segmentation Via Integrating Mass Spectrometry Imaging and Hematoxylin-Erosin Stained Histopathological Image

Mass Spectrometry Imaging (MSI) provides a useful tool to divide a tissue section into sub-regions with similar molecular profiles, namely tissue segmentation. However, owing to the lack of ground truth, there is no reliable evaluation approach to assess the validity of unsupervised segmentation outcomes of MSI. We propose a novel solution grounded on a presumption that a segmentation is reliable if it can be reproduced using distinct bio-information extracted from independent sources. Specifically, besides molecular information from MSI data, we also obtain morphological information over a tissue section from its Hematoxylin-Erosin (H&E) stained histopathological image. MSI has high molecular specificity but low spatial resolving power, the H&E image has no molecular specificity but it can capture microscopic details of the tissue with a spatial resolution two magnitudes higher than MSI. The whole H&E image is split into an array of small patches, which correspond to the spatial pixels of MSI. A spectrum of informative morphological features is computed iteratively for each patch and spatial segmentation can be generated by clustering the patches based on their morphological similarities. Adjusted Mutual Information (AMI) score measures the degree of agreement between MSI-based and H&E image-based segmentation outcomes, which is defined by us as an objective and quantitative evaluation metric of segmentation validity. We investigated various candidate morphological features: a combination of Deep Convolution Neural Network (DCNN) features and handcrafted Threshold Adjacency Statistics (TAS) features finally stood out. The most appropriate number of tissue segments was also determined according to AMI score. Moreover, we introduced Co-Clustering algorithm to MSI data to simultaneously group m/z variables and spatial pixels, so potential biomarkers associated to each sub-region were discovered without the need of further analysis. Eventually, by integrating the segmentation outcomes based on MSI and H&E image data, the confidence level of the segment assignment was displayed for each pixel, which offered a much more informative and compelling way to present the segmentation results.
A novel telencephalon-opto-hypothalamic morphogenetic domain produces most of the glutamatergic neurons of the medial extended amygdala

Deficits in social cognition and behavior are a hallmark of many psychiatric disorders. The medial extended amygdala, including the medial amygdala and the medial bed nucleus of the stria terminalis, is a key component of functional networks involved in sociality. However, this nuclear complex is highly heterogeneous and contains numerous GABAergic and glutamatergic neuron subpopulations. Deciphering the connections of different neurons is essential in order to understand how this structure regulates different aspects of sociality, and it is necessary to evaluate their differential implication in distinct mental disorders. Developmental studies in different vertebrates are offering new venues to understand neuronal diversity of the medial extended amygdala, and are helping to establish a relation between the embryonic origin and molecular signature of distinct neurons with the functional subcircuits in which they are engaged. These studies have provided many details on the distinct GABAergic neurons of the medial extended amygdala, but information on the glutamatergic neurons is still scarce. Using an Otp-eGFP transgenic mouse and multiple fluorescent labeling, we show that most glutamatergic neurons of the medial extended amygdala originate in a novel telencephalo-opto-hypothalamic embryonic domain (TOH), located at the transition between telencephalon and hypothalamus, which produces Otp-lineage neurons expressing the telencephalic marker Foxg1 but not Nkx2.1 during development. These glutamatergic cells include a subpopulation of projection neurons of the medial amygdala, which activation has been previously shown to promote autistic-like behavior. Our data open new venues for studying the implication of this neuron subtype in neurodevelopmental disorders producing social deficits.
The First Mitotic Division of the Human Embryo is Highly Error-prone

Aneuploidy in human embryos is surprisingly prevalent and increases drastically with maternal age, resulting in miscarriages, infertility and birth defects. Frequent errors during the meiotic divisions cause this aneuploidy, while age-independent errors during the first cleavage divisions of the embryo also contribute. However, the underlying mechanisms are poorly understood, largely because these events have never been visualised in living human embryos. Here, using cell-permeable DNA dyes, we film chromosome segregation during the first and second mitotic cleavage divisions in human embryos from women undergoing assisted reproduction following ovarian stimulation. We show that the first mitotic division takes several hours to complete and is highly variable. Timings of key mitotic events were, however, largely consistent with clinical videos of embryos that gave rise to live births. Multipolar divisions and lagging chromosomes during anaphase were frequent with no maternal age association. In contrast, the second mitosis was shorter and underwent mostly bipolar divisions with no detectable lagging chromosomes. We propose that the first mitotic division in humans is a unique and highly error-prone event, which contributes to fetal aneuploidies.
The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing

Natural killer (NK) cells are innate immune lymphocytes capable of killing target cells without prior sensitization. NK cell activity is regulated by signals received from activating and inhibitory receptors. One pivotal activating NK receptor is NKG2D, which binds a family of eight ligands, including the major histocompatibility complex (MHC) class I-related chain A (MICA). Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus causing morbidity and mortality in immunosuppressed patients and congenitally infected infants. HCMV encodes multiple antagonists of NK cell activation, including many mechanisms targeting MICA. However, only one of these mechanisms counters the most prevalent MICA allele, MICA*008. Here, we discover that a hitherto uncharacterized HCMV protein, UL147A, specifically targets MICA*008 to proteasomal degradation, thus hindering the elimination of HCMV-infected cells by NK cells. Mechanistic analyses disclose that the non-canonical GPI anchoring pathway of immature MICA*008 constitutes the determinant of UL147A specificity for this MICA allele. These findings advance our understanding of the complex and rapidly evolving HCMV immune evasion mechanisms, which may facilitate the development of antiviral drugs and vaccines. Author Summary Human cytomegalovirus (HCMV) is a common pathogen that usually causes asymptomatic infection in the immunocompetent population, but the immunosuppressed and fetuses infected in utero suffer mortality and disability due to HCMV disease. Current HCMV treatments are limited and no vaccine has been approved, despite significant efforts. HCMV encodes many genes of unknown function, and virus-host interactions are only partially understood. Here, we discovered that a hitherto uncharacterized HCMV protein, UL147A, downregulates the expression of an activating immune ligand allele named MICA*008, thus hindering the elimination of HCMV-infected cells. Elucidating HCMV immune evasion mechanisms could aid in the development of novel HCMV treatments and vaccines. Furthermore, MICA*008 is a highly prevalent allele implicated in cancer immune evasion, autoimmunity and graft rejection. In this work we have shown that UL147A interferes with MICA*008’s poorly understood, nonstandard maturation pathway. Study of UL147A may enable manipulation of its expression as a therapeutic measure against HCMV.
Genomic prediction in the wild: A case study in Soay sheep

Genomic prediction, the technique whereby an individual’s genetic component of their phenotype is estimated from its genome, has revolutionised animal and plant breeding and medical genetics. However, despite being first introduced nearly two decades ago, it has hardly been adopted by the evolutionary genetics community studying wild organisms. Here, genomic prediction is performed on eight traits in a wild population of Soay sheep. The population has been the focus of a >30 year evolutionary ecology study and there is already considerable understanding of the genetic architecture of the focal Mendelian and quantitative traits. We show that the accuracy of genomic prediction is high for all traits, but especially those with loci of large effect segregating. Five different methods are compared, and the two methods that can accommodate zero-effect and large-effect loci in the same model tend to perform best. If the accuracy of genomic prediction is similar in other wild populations, then there is a real opportunity for pedigree-free molecular quantitative genetics research to be enabled in many more wild populations; currently the literature is dominated by studies that have required decades of field data collection to generate sufficiently deep pedigrees. Finally, some of the potential applications of genomic prediction in wild populations are discussed.
Agrilus quercicola (Fisher) (Coleoptera: Buprestidae), the Gambel Oak Borer, as a Pest of Quercus spp.

Abstract. During 2003 an unusual outbreak of the Gambel oak borer, Agrilus quercicola (Fisher), caused extensive damage to several species of oak in Denver, Araphaoe, and Douglas counties in Colorado. This followed several seasons of environmental stress that predisposed Gambel oak to the insect, but adults apparently dispersed more than 30 km during this outbreak to kill oaks a considerable distance from native Gambel oak stands. In choice tests, adults fed on foliage of Gambel oak, but not other herbaceous shrubs common in stands of Gambel oak. Yellow and neon yellow-green, but not white, sticky traps caught considerable numbers of adults. Adult flight activity began in late May, peaked in early summer, and ended in late August. A chalcid parasitoid, Phasgonophora sulcata Westwood, was noted to be an important natural enemy. No injury by this insect has been observed outside of native Gambel oak in years subsequent to the 2003 outbreak.
Métodos para quebra de dormência de unidades de dispersão de Zizyphus joazeiro Mart. (Rhamnaceae)

Z. joazeiro is a forest species of great socioeconomic importance for the Brazilian Northeast region, but of difficult germination caused by the water impermeability of dispersal units. The present study evaluated pre-germinative treatments for overcoming dormancy in Zizyphus joazeiro seeds. The experiment was carried out in greenhouse conditions at Centro de Ciencias Agrarias, Universidade Federal da Paraiba, Areia-PB, Brazil. The treatments were as follow: control (intact dispersal units), mechanical scarification with sandpaper, immersion in water at room temperature for 24, 48, 72, 96 and 120 hours, immersion in water at 70 C for three minutes and, immersion in concentrated sulfuric acid for 30, 60, 90, 120 and 150 minutes. The evaluated variables included emergence percentage, first count and emergence speed index, length and weight of plant dry matter. The treatments showing higher Z. joazeiro seedling emergence were immersion of dispersal units in cold water for 48 hours, immersion in water at 70 C for three minutes and manual scarification with sandpaper, overcoming tegument hardness in dispersal units of this species.