Miracle-dz/UniFAR-FTUs huggingface dataset:
Thalamic spindles and upstates, but not ripples, coordinate cortico-cortical and hippocampo-cortical co-ripples in humans

The co-occurrence of brief ∼90Hz oscillations (co-ripples) may be important for integrating information across the neocortex and hippocampus and, therefore, essential for sleep consolidation, and cognition in general. However, how such co-ripples are synchronized is unknown. We tested if cortico-cortical and hippocampal-cortical ripple co-occurrences are due to the simultaneous direct propagation of thalamic ripples, and/or if they are coordinated by lower frequency thalamic waves. Using human intracranial recordings, we found that ripples are generated in the anterior and posterior thalamus during local spindles on the down-to-upstate transition in non-rapid eye movement sleep, with similar characteristics as cortical and hippocampal ripples. However, thalamic ripples only infrequently co-occur or phase-lock, with cortical and hippocampal ripples. In contrast, thalamo-cortical spindles and upstates were strongly coordinated with cortico-cortical and hippocampo-cortical co-rippling. Thus, while thalamic ripples may not directly drive multiple cortical or hippocampal sites at ripple frequency, thalamo-cortical spindles and upstates may provide the input necessary for spatially distributed co-rippling to integrate information in the cortex. Significance Statement Widespread networks of ∼90 Hz oscillations, called “ripples,” have recently been identified in humans and may help to bind information in the cortex and hippocampus for memory. However, it is not known whether the thalamus generates ripples, and if so whether they, or other thalamic waves, coordinate networks of co-occurring cortical and hippocampal ripples. Here, we show that the human thalamus generates ∼90 Hz ripples during NREM sleep. While thalamic ripples do not appear to directly synchronize ripple co-occurrence in the cortex and hippocampus, our data provide evidence that propagating thalamo-cortical spindles and upstates organize these networks. Thus, the thalamus projects slower frequency waves that modulate higher frequency hippocampo-cortical oscillatory networks for memory in humans.
This population does not exist: learning the distribution of evolutionary histories with generative adversarial networks

Numerous studies over the last decade have demonstrated the utility of machine learning methods when applied to population genetic tasks. More recent studies show the potential of deep learning methods in particular, which allow researchers to approach problems without making prior assumptions about how the data should be summarized or manipulated, instead learning their own internal representation of the data in an attempt to maximize inferential accuracy. One type of deep neural network, called Generative Adversarial Networks (GANs), can even be used to generate new data, and this approach has been used to create individual artificial human genomes free from privacy concerns. In this study, we further explore the application of GANs in population genetics by designing and training a network to learn the statistical distribution of population genetic alignments (i.e. data sets consisting of sequences from an entire population sample) under several diverse evolutionary histories—the first GAN capable of performing this task. After testing multiple different neural network architectures, we report the results of a fully differentiable Deep-Convolutional Wasserstein GAN with gradient penalty that is capable of generating artificial examples of population genetic alignments that successfully mimic key aspects of the training data, including the site frequency spectrum, differentiation between populations, and patterns of linkage disequilibrium. We demonstrate consistent training success across various evolutionary models, including models of panmictic and subdivided populations, populations at equilibrium and experiencing changes in size, and populations experiencing either no selection or positive selection of various strengths, all without the need for extensive hyperparameter tuning. Overall, our findings highlight the ability of GANs to learn and mimic population genetic data and suggest future areas where this work can be applied in population genetics research that we discuss herein.
An intragenic FAT1 regulatory element deleted in muscular dystrophy patients drives muscle and mesenchyme expression during development

Fat1 is an atypical cadherin playing multiple roles that influence tissue morphogenesis. During mouse development Fat1 is required to modulate muscle morphogenesis through complementary activities in myogenic cells, muscle-associated connective tissue, and motor neurons, ablation of which leads to regionalized muscle phenotypes. We previously identified copy number variants (CNV) deleting an intragenic conserved non-coding element (CNE) in the human FAT1 locus, that were enriched among muscular dystrophy patients with symptoms resembling those of Facioscapulohumeral Dystrophy (FSHD), compared to healthy individuals. Since such deletions of a putative cis-regulatory element had the potential to cause tissue-specific depletion of FAT1, they were postulated to act as symptom modifiers. However, activity of this CNE has not been functionally explored so far. To investigate the possible regulatory activity of this Fat1-CNE, we engineered transgenic mice in which it drives expression of a bi-cistronic reporter comprising the CRE-recombinase (Cre) and a myristilated-tdTomato fluorescent protein. The tissue-specific pattern of cre and tomato expression indicates that this enhancer has bipotential character, and drives expression in skeletal muscle and in muscle-associated mesenchymal cells. We extended our analysis of one of the transgenic lines, which exhibits enhanced expression in mesenchymal cells at extremities of subsets of muscles matching the map of Fat1-dependent muscles. This transgenic line exhibits highly selective CRE-mediated excision in scattered cells within the Tomato-positive territory hotspots. This represents a novel tool to genetically explore the diversity of muscle-associated mesenchymal lineages.
An R-R-type MYB transcription factor promotes nonclimacteric pepper fruit ripening pigmentation

Carotenoids act as phytohormones and volatile compound precursors that influence plant development and confer characteristic colours, affecting both the aesthetic and nutritional value of fruits. Carotenoid pigmentation in ripening fruits is highly dependent on developmental trajectories. Transcription factors incorporate developmental and phytohormone signalling to regulate the biosynthesis process. In contrast to the well-established pathways regulating ripening-related carotenoid biosynthesis in climacteric fruit, carotenoid regulation in nonclimacteric fruit is poorly understood. Capsanthin is the primary carotenoid of nonclimacteric pepper (Capsicum) fruit; its biosynthesis is tightly associated with fruit ripening, and it confers red pigment to the ripening fruit. In this study, using a weighted gene coexpression network and expression analysis, we identified an R-R-type MYB transcription factor, DIVARICATA1, and demonstrated that it is tightly associated with the levels of carotenoid biosynthetic genes (CBGs) and capsanthin accumulation. DIVARICATA1 encodes a nucleus-localized protein that functions primarily as a transcriptional activator. Functional analyses demonstrated that DIVARICATA1 positively regulates CBG transcript levels and capsanthin contents by directly binding to and activating the CBG promoter transcription. Furthermore, the association analysis revealed a significant positive association between DIVARICATA1 transcription level and capsanthin content. Abscisic acid (ABA) promotes capsanthin biosynthesis in a DIVARICATA1-dependent manner. Comparative transcriptomic analysis of DIVARICATA1 in pepper and its orthologue in a climacteric fruit, tomato, suggests that its function might be subject to divergent evolution among the two species. This study illustrates the transcriptional regulation of capsanthin biosynthesis and offers a novel target for breeding peppers with high red colour intensity.
Neurofibromin 1 mediates sleep depth in Drosophila

Neural regulation of sleep and metabolic homeostasis are critical in many aspects of human health. Despite extensive epidemiological evidence linking sleep dysregulation with obesity, diabetes, and metabolic syndrome, little is known about the neural and molecular basis for the integration of sleep and metabolic function. The RAS GTPase-activating gene Neurofibromin (Nf1) has been implicated in the regulation of sleep and metabolic rate, raising the possibility that it serves to integrate these processes, but the effects on sleep consolidation and physiology remain poorly understood. A key hallmark of sleep depth in mammals and flies is a reduction in metabolic rate during sleep. Here, we use indirect calorimetry to define the role of Nf1 on sleep-dependent changes in metabolic rate. Flies lacking Nf1 fail to suppress metabolic rate during sleep, raising the possibility that loss of Nf1 prevents flies from integrating sleep and metabolic state. Sleep of Nf1 mutant flies is fragmented with a reduced arousal threshold in Nf1 mutants, suggesting Nf1 flies fail to enter deep sleep. The effects of Nf1 on sleep can be localized to a subset of neurons expressing the GABA receptor Rdl. Selective knockdown of Nf1 in Rdl-expressing neurons increases gut permeability and reactive oxygen species (ROS) in the gut, suggesting a critical role for deep sleep in gut homeostasis. Together, these findings suggest Nf1 acts in GABA-sensitive neurons to modulate sleep depth in Drosophila.
MEF2A suppresses replicative stress responses that trigger DDX41-dependent IFN production

Interferons (IFN) are induced by sensing of self- and non-self DNA or genomic lesions by pathogen recognition receptors (PRR) that activate STING. These pathways must be kept in check by negative regulators to prevent unscheduled activation of IFN, which contributes to autoinflammation. Here we show that MEF2A as a novel negative regulator of inflammation that suppresses homeostatic induction of IFNs. Indeed, MEF2A deficiency results in the spontaneous production of type I IFN and robust downstream IFN-stimulated gene expression that coincided with a robust cellular antiviral state. Mechanistically, MEF2A depletion promoted the accumulation of R-loops that activate the DDX41/STING pathway. This pro-inflammatory pathway was dependent on ATR kinase activity, hallmark of the replicative stress response, was necessary for the activation of STING upon loss of MEF2A expression. Thus, our study connects MEF2A with protection from maladaptive type I IFN responses triggered by R-loop accumulation and links the DDX41-dependent activation of STING to the DNA damage response.
Inhibitory and in silico molecular docking of Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa phytochemical compounds on human α-glucosidases

Ethnopharmacological relevance Herbal traditional medicine is used by millions of people in Africa for treatment of ailments such as diabetes mellitus, stomach disorders and respiratory diseases. Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa (X. stuhlmannii (Taub.)) is a medicinal plant used traditionally in Zimbabwe to treat type 2 diabetes mellitus (T2DM) and its complications. However, there is no scientific evidence to support its inhibitory effect against digestive enzymes (α-glucosidases) that are linked to high blood sugar in humans. Aim of the study : This work aims to investigate whether bioactive phytochemicals of crude X. stuhlmannii (Taub.) can scavenge free radicals and inhibit α-glucosidases in order to reduce blood sugar in humans. Materials and methods Here we examined the free radical scavenging potential of crude aqueous, ethyl acetate and methanolic extracts of X. stuhlmannii (Taub.) using the diphenyl-2-picrylhydrazyl assay in vitro. Furthermore, we carried out in vitro inhibition of α-glucosidases (α-amylase and α-glucosidase) by the crude extracts using chromogenic 3,5-dinitrosalicylic acid and p-nitrophenyl-α-D-glucopyranoside substrates. We also used molecular docking approaches (Autodock Vina) to screen for bioactive phytochemical compounds targeting the digestive enzymes. Results Our results showed that phytochemicals in X. stuhlmannii (Taub.) aqueous, ethyl acetate and methanolic extracts scavenged free radicals with IC50 values ranging from 0.002-0.013 μg/mL. Furthermore, crude aqueous, ethyl acetate and methanolic extracts significantly inhibited α-amylase and α-glucosidase with IC50 values of 10.5-29.5 μg/mL (versus 54.1±0.7 μg/mL for acarbose) and 8.8-49.5 μg/mL (versus 161.4±1.8 μg/mL for acarbose), respectively. In silico molecular docking findings and pharmacokinetic predictions showed that myricetin is likely a novel plant-derived α-glucosidase inhibitor. Conclusion Collectively, our findings suggest pharmacological targeting of digestive enzymes by X. stuhlmannii (Taub.) crude extracts may reduce blood sugar in humans with T2DM via inhibition of α-glucosidases.
Effects of social presence on behavioural, neural and physiological aspects of empathy for pain

In mediated interactions (e.g. video calls), less information is available about the other. To investigate how this affects our empathy for one another, we conducted an EEG study, in which thirty human participants observed one of 5 targets undergoing painful electric stimulation, once in a direct interaction and once in a live, video-mediated interaction. We found that observers were as accurate in judging others’ pain and showed as much affective empathy via video as in a direct encounter. While mu suppression, a common neural marker of empathy, was not sensitive to others’ pain, theta responses to others’ pain as well as skin conductance coupling between participants were reduced in the video-mediated condition. We conclude that physical proximity with its rich social cues is important for nuanced physiological resonance with the other’s experience. More studies are warranted to confirm these results and to understand their behavioural significance for remote social interactions.
Seeing speech: The cerebral substrate of tickertape synesthesia

Reading acquisition is enabled by deep changes in the brain’s visual system and language areas, and in the links subtending their collaboration. Disruption of those plastic processes commonly results in developmental dyslexia. However, atypical development of reading mechanisms may occasionally result in ticker-tape synesthesia (TTS), a condition described by Francis Galton in 1883 wherein individuals “see mentally in print every word that is uttered (…) as from a long imaginary strip of paper”. While reading is the bottom-up translation of letters into speech, TTS may be viewed as its opposite, the top-down translation of speech into internally visualized letters. In a series of functional MRI experiments, we studied MK, a man with TTS. We showed that a set of left-hemispheric areas were more active in MK than in controls during the perception of normal than reversed speech, including frontoparietal areas involved in speech processing, and the Visual Word Form Area, an occipitotemporal region subtending orthography. Those areas were identical to those involved in reading, supporting the construal of TTS as upended reading. Using dynamic causal modeling, we further showed that, parallel to reading, TTS induced by spoken words and pseudowords relied on top-down flow of information along distinct lexical and phonological routes, involving the middle temporal and supramarginal gyri, respectively. Future studies of TTS should shed new light on the neurodevelopmental mechanisms of reading acquisition, their variability and their disorders. Significance statement Some individuals, whenever they are hearing speech, see vividly in their mind’s eye the corresponding words in written form, as mental subtitles. This unusual condition, termed ticker-tape synesthesia (TTS), far from being purely anecdotal, actually touches on the core of the brain mechanisms of normal and impaired reading acquisition. Through 3 fMRI experiments, plus brain connectivity analyses, we propose an in-depth study of a single individual with such ticker-tape synesthesia. We propose that TTS, a situation in some sense symmetrical to developmental dyslexia, reflects an inverted flow of information through the reading system, such that speech is automatically translated into internally visualized letters. Future studies of TTS should shed new light on the neurodevelopmental mechanisms of reading acquisition.
Diverse transcriptomic response of cellular system following low-dose exposure of mesoporous nanoparticles

Mesoporous nanoparticles (NPs) are an interesting drug delivery system that has generated considerable attention in the biomedical sector. Despite recent attempts to conduct safety assessments using traditional methods based on phenotypic data, our understanding of the underlying molecular processes produced by mesoporous NPs is still in its infancy. In the present study, RNA sequencing was used to assess the biological perturbations and the pathways induced in response to early exposure of two different mesoporous NPs; mesoporous silica NPs (MSN) and mesoporous carbon NPs (MCN) in human liver hepatocellular carcinoma cells. In order to better understand the risks associated with NPs, it is required to consider the initial low-dose exposure effects that mimic the real exposure scenario. No overt toxicity was detected in the MTT assay when performed at 6 hours at low concentrations (MCN 25 g/ml and MSN 15 g/ml) of NPs; thus, we have selected this dose for RNA sequencing analysis. Our transcriptomics analysis showed significant differences in the expression of many genes after exposure to both NPs. Surprisingly, both NPs frequently deregulated 52.9 percent of upregulated and 42 percent of downregulated genes. Gene ontology categories, in particular, revealed comparable perturbations of biological reactions in the cellular system. HepG2 cells reacted to mesoporous NPs by allowing alterations in genes involved in cytoskeleton reorganisation (ATAT1, DMTN, PTK2 and PFN2). Exposure to mesoporous NPs increased transcripts expressing ubiquitin ligase (RNF187, ARIH2, VHL, and RAB40C), transferase (FBXO3 and WDSUB1), conjugating (UBE2J2), and also proteasomal subunits (PSMD2, PSMD13) enzymes, indicating that protein turnover rates are altered in response to environmental damage. In addition, DNA damage and DNA damage checkpoint genes were upregulated, indicating that NPs induced stress in the cells. These finding showed low dosage acute exposure have comparable responses between mesoporous NPs. These results may add further knowledge in conceptualization of Safer-by-Design strategy of NPs in biomedical field.
Development of the first high-density linkage map in the maize weevil, Sitophilus zeamais

The maize weevil, Sitophilus zeamais, is a worldwide pest that disproportionately affects subsistence farmers in developing countries. Damage from this pest threatens food security in these communities as widely available and effective control methods are lacking. With advances over the last decade in the development of advanced genetic pest management techniques, addressing pest issues at the ecosystem level as opposed to the farm level may be a possibility. However, pest species selected for genetic management techniques require a well-characterized genome and few genomic tools have been developed for maize weevil. Here, we have measured the genome size and developed the first genetic linkage map for this species. The genome size was determined using flow cytometry as 682 Mb and 674 Mb for females and males, respectively. The linkage map contains 11 linkage groups, which correspond to the 10 autosomes and 1 X-chromosome found in the species and it contains 1,121 SNPs. This linkage map will be useful for assembling a complete genome for maize weevil.
Gamma Rays Observed from 100-MeV Protons Interacting with Fe 56 and Ni 58

Gamma radiation from 100-MeV protons incident on targets of $^{58}\mathrm{Ni}$ and $^{56}\mathrm{Fe}$ has been observed. Residual nuclei were identified by using the known $\ensuremath{\gamma}$ rays. Some of the strongest $\ensuremath{\gamma}$ rays observed involved residual nuclei equivalent to the target nucleus minus one to three $\ensuremath{\alpha}$ particles. These results can be understood on the basis of a pre-equilibrium stage involving an intranuclear nucleon-nucleon cascade followed by an evaporation process.
TNF and HNRNPL Related Immunoregulatory Long non-coding RNA (THRIL) and long intergenic noncoding RNA-p21 (lincRNA-p21) as potential useful biomarkers for the diagnosis of tuberculosis

Early diagnosis is crucial in controlling tuberculosis globally and in developing countries with the emergence of drug-resistant Mycobacterium tuberculosis strains. Long non-coding RNAs (lncRNAs) are promising tuberculosis diagnostic biomarkers. Two lncRNA diagnostic markers, lncRNA THRIL and lincRNA-p21, were studied as tuberculosis diagnostic biomarkers. This cross-sectional study was conducted at the Center of Respiratory Diseases of LAQUINTINIE hospital and the National Veterinary Laboratory of Douala from December 2020 to August 2021. The ability of lncRNAs to distinguish between 19 healthy controls, 15 latent tuberculosis, and 21 active tuberculosis was estimated using quantitative polymerase chain reaction and Receiver Operating Characteristic curve analysis. Our analysis showed that lncRNA THRIL and lincRNA-p21 were significantly upregulated (P <0.05) in active and latent tuberculosis compared with healthy controls. LincRNA-p21 expression was significantly increased (P <0.05) in active tuberculosis compared with latent tuberculosis, whereas lncRNA THRIL was not significantly affected (P ≥0.05). Both lncRNA THRIL and lincRNA-p21 showed excellent performance in classifying latent tuberculosis and healthy controls (AUC = 92.86%). Furthermore, lncRNA THRIL was good at discriminating active tuberculosis from healthy controls (AUC = 89.79%), while lincRNA-p21 showed excellent discriminating performance (AUC = 100%). LncRNA THRIL was identified as a poor discriminator of latent tuberculosis from active tuberculosis (AUC = 64.28%), while lincRNA-p21 showed excellent diagnostic performance in this distinction (AUC = 92.86%). Our cross-sectional study suggests that lncRNA THRIL and lincRNA-p21 are promising tuberculosis diagnostic biomarkers that can differentiate between latent and active infection.