Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidental temporal binding in rats: A novel behavioral task

We designed a behavioral task called One-Trial Trace Escape Reaction (OTTER), in which rats incidentally associate two temporally discontinuous stimuli: a neutral acoustic cue (CS) with an aversive stimulus (US) which occurs two seconds later (CS-2s-US sequence). Rats are first habituated to two similar environmental contexts (A and B), each consisting of an interconnected dark and light chamber. Next, rats experience the CS-2s-US sequence in the dark chamber of one of the contexts (either A or B); the US is terminated immediately after a rat escapes into the light chamber. The CS-2s-US sequence is presented only once to ensure the incidental acquisition of the association. The recall is tested 24 h later when rats are presented with only the CS in the alternate context (B or A), and their behavioral response is observed. Our results show that 59 % of the rats responded to the CS by escaping to the light chamber, although they experienced only one CS-2s-US pairing. The OTTER task offers a flexible high throughput tool to study memory acquired incidentally after a single experience. Incidental acquisition of association between temporally discontinuous events is highly relevant to episodic memory formation.
Multimodal Object Representations Rely on Integrative Coding

Combining information from multiple senses is essential to object recognition. Yet how the mind combines sensory input into coherent multimodal representations – the multimodal binding problem – remains poorly understood. Here, we applied multi-echo fMRI across a four-day paradigm, in which participants learned 3-dimensional multimodal object representations created from well-characterized visual shape and sound features. Our novel paradigm decoupled the learned multimodal object representations from their baseline unimodal shape and sound features, thus tracking the emergence of multimodal concepts as they were learned by healthy adults. Critically, the representation for the whole object was different from the combined representation of its individual parts, with evidence of an integrative object code in anterior temporal lobe structures. Intriguingly, the perirhinal cortex – an anterior temporal lobe structure – was by default biased towards visual shape, but this initial shape bias was attenuated with learning. Pattern similarity analyses suggest that after learning the perirhinal cortex orthogonalized combinations of visual shape and sound features, transforming overlapping feature input into distinct multimodal object representations. These results provide evidence of integrative coding in the anterior temporal lobes that is distinct from the distributed sensory features, advancing the age-old question of how the mind constructs multimodal objects from their component features.
Successive phase transitions at finite temperatures toward the supersolid state in a three-dimensional extended Bose-Hubbard model

We study the finite temperature properties of the extended Bose-Hubbard model on a cubic lattice. This model exhibits the so-called supersolid state. To start with, we investigate the ground-state phase diagram and find the supersolid state in the region of underdoped (less than the half-filled) density in contrast to the cases of one- and two-dimensional systems where the superfluid state and the solid state show the phase separation. Next, we investigate ordering processes at finite temperatures by quantum Monte Carlo simulations and find successive superfluid and solid phase transitions. There, we find that the two order parameters compete with each other. We establish a finite temperature phase diagram, which contains the superfluid, the solid, the supersolid, and the disordered phases. We develop a mean-field theory to analyze the ordering processes and compare the result with that obtained by simulations and discuss the mechanism of the competition of these two orders. We also study how the supersolid region shrinks as the on-site repulsion becomes strong.
The variation of rotation curve shapes as a signature of the effects of baryons on dark matter density profiles

Rotation curves of galaxies show a wide range of shapes, which can be paramaterized as scatter in Vrot(1kpc)/Vmax i.e.the ratio of the rotation velocity measured at 1kpc and the maximum measured rotation velocity. We examine whether the observed scatter can be accounted for by combining scatters in disc scale-lengths, the concentration-halo mass relation, and the M*-Mhalo relation. We use these scatters to create model galaxy populations; when housed within dark matter halos that have universal, NFW density profiles, the model does not match the lowest observed values of Vrot(1kpc)/Vmax and has too little scatter in Vrot(1kpc)/Vmax compared to observations. By contrast, a model using a mass dependent dark matter profile, where the inner slope is determined by the ratio of M*/Mhalo, produces galaxies with low values of Vrot(1kpc)/Vmax and a much larger scatter, both in agreement with observation. We conclude that the large observed scatter in Vrot(1kpc)/Vmax favours density profiles that are significantly affected by baryonic processes. Alternative dark matter core formation models such as SIDM may also account for the observed variation in rotation curve shapes, but these observations may provide important constraints in terms of core sizes, and whether they vary with halo mass and/or merger history.
Myoglobin promotes cardiomyocyte differentiation through oxidatively modulating the Hippo Kinase Pathway

Background While cardiomyocytes undergo terminal differentiation postnatally and rarely re-enter the cell cycle, the endogenous mechanisms that propagate differentiation and prevent de-differentiation remain unclear. The monomeric heme protein myoglobin, which stores oxygen and regulates reactive oxygen/nitrogen species balance in the heart, increases in expression by over 50% during cardiomyocyte differentiation. Though myoglobin deletion without significant compensation is embryonic lethal in mice, a role for the protein in regulating cardiomyocyte differentiation has not been tested. We hypothesized that myoglobin expression is required for cardiomyocyte differentiation and the loss of myoglobin enables de-differentiation. Methods Myoglobin was genetically silenced in HL-1, H9C2 cells, and neonatal rat ventricular cardiomyocytes (NRVM) to examine myoglobin-dependent effects on differentiation, proliferation, and Hippo pathway signaling. A zebrafish model of Mb depletion was made using CRISPR-Cas9 to test the effect of myoglobin depletion on cardiac regeneration after apical resection injury in vivo. Results Myoglobin deletion in cultured cell lines and NRVM decreased the gene expression of cardiomyocyte differentiation markers (troponin, myosin light chain, and myosin heavy chain), upregulated markers of dedifferentiation (runx1 and dab2) and stimulated cell proliferation. Mechanistically, we show that the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, which activates the enzyme to phosphorylate the downstream Yes-associated protein (YAP) transcription factor, which prevents its transcriptional activity. Thus, the loss of myoglobin results in the de-phosphorylation and nuclear translocation of YAP, which propagates proliferation and fetal gene expression. In vivo, myoglobin-deficient zebrafish hearts recapitulated the increase in YAP signaling and showed accelerated regeneration at 20 days post apical injury. Conclusion We a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation, and a regulator of the Hippo pathway. These findings suggest myoglobin as a potential target for strategies to enhance cardiac development and improve cardiac repair and regeneration.
SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b

The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding - prevented PKR activation, inhibited β-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Similar observations were made for the N protein of human coronavirus 229E, suggesting that this may be a general trait conserved among members of other orthocoronavirus (sub)genera. SIGNIFICANCE STATEMENT SARS-CoV-2 nucleocapsid protein N is an antagonist of innate immunity but how it averts virus detection by intracellular sensors remains subject to debate. We provide evidence that SARS-CoV-2 N, by sequestering dsRNA through domain N2b, prevents PKR-mediated activation of the integrated stress response as well as detection by RIG-I-like receptors and ensuing type I interferon expression. This function, conserved in human coronavirus 229E, is not affected by mutations that prevent posttranslational modifications, previously implicated in immune evasion, or that target its binding to stress granule scaffold proteins. Our findings further our understanding of how SARS-CoV-2 evades innate immunity, how this may drive viral evolution and why increased N expression may have been a selective advantage to SARS-CoV-2 variants of concern.
The condensin II/TOP-2 axis silences transcription during germline specification in C. elegans

In C. elegans, the germline is specified via a preformation mechanism that relies on the PIE-1 protein’s ability to globally silence mRNA transcription in germline precursor cells, also known as the P-lineage. Recent work from our group has identified additional genome silencing events in C. elegans, during oogenesis and in starved L1 larvae, and these require the condensin II complex, topoisomerase II (TOP-2), and components of the H3K9me/heterochromatin pathway. Interestingly, silencing in oocytes also requires PIE-1, but this is not the case in starved L1s. Here, we ask if additional genome silencing components besides PIE-1 are required to repress gene expression in the P-lineage of early embryos, and we find that condensin II and TOP-2 are required and the H3K9me/heterochromatin pathway is not. We show that depletion of condensin II/TOP-2 activates the normally suppressed RNA polymerase II to inappropriately transcribe somatic genes in the P-lineage. We also present evidence that while both PIE-1 and condensin II/TOP-2 are required for genome silencing in the P-lineage, PIE-1 can silence transcription independently of condensin II/TOP-2 when misexpressed in somatic cells. Thus, in oocytes all three genome silencing systems (TOP-2/condensin II, H3K9me, and PIE-1) are operational while in both early embryos and starved L1s two of the three that are active (TOP-2/condensin II and PIE-1 for early embryos, TOP-2/condensin II and H3K9me for starved L1s). Our data show that multiple, redundantly acting genome silencing mechanisms act in a mix and match manner to repress transcription at different developmental stages in the C. elegans germline.
Synthetic genotype networks

Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. They facilitate evolutionary innovation by enabling the exploration of different neighborhoods in genotype space. Genotype networks, first suggested by theoretical models, have been empirically confirmed for proteins and RNAs. Comparative studies also support their existence for gene regulatory networks (GRNs), but direct experimental evidence is lacking. Here, we report the construction of three interconnected genotype networks of synthetic GRNs producing three distinct gene expression phenotypes in Escherichia coli. These genotype networks, composed of over twenty different synthetic GRNs, provide robustness in face of mutations while enabling transitions to innovative phenotypes. Through realistic mathematical modeling, we quantify robustness and evolvability for the complete genotype-phenotype map and link these features mechanistically to GRN motifs. Our work thereby exemplifies how GRN evolution along genotype networks might be driving evolutionary innovation.
Machine learning identification of Pseudomonas aeruginosa strains from colony 1 image data 2

21 When grown on agar surfaces, microbes can produce distinct multicellular spatial structures called 22 colonies, which contain characteristic sizes, shapes, edges, textures, and degrees of opacity and 23 color. For over one hundred years, researchers have used these morphology cues to classify 24 bacteria and guide more targeted treatment of pathogens. Advances in genome sequencing 25 technology have revolutionized our ability to classify bacterial isolates and while genomic 26 methods are in the ascendancy, morphological characterization of bacterial species has made a 27 resurgence due to increased computing capacities and widespread application of machine learning 28 tools. In this paper, we revisit the topic of colony morphotype on the within-species scale and 29 apply concepts from image processing, computer vision, and deep learning to a dataset of 69
Impact on S. aureus and E. coli membranes of treatment with chlorhexidine and alcohol solutions: insights from molecular simulations and nuclear magnetic resonance

Membranes form the first line of defence of bacteria against potentially harmful molecules in the surrounding environment. Understanding the protective properties of these membranes represents an important step towards development of targeted anti-bacterial agents such as sanitizers. Use of propanol, isopropanol and chlorhexidine can significantly decrease the threat imposed by bacteria in the face of growing anti-bacterial resistance via mechanisms that include membrane disruption. Here we have employed molecular dynamics simulations and nuclear magnetic resonance to explore the impact of chlorhexidine and alcohol on the S. aureus cell membrane, as well as the E. coli inner and outer membranes. We identify how sanitizer components partition into these bacterial membranes, and show that chlorhexidine is instrumental in this process.
Walk the Plank! Using mobile EEG to investigate emotional lateralization of immersive fear in virtual reality

Most studies on emotion processing rely on the presentation of emotional images or films. However, this methodology lacks ecological validity, limiting the extent to which findings can generalize to emotion processing in the wild. More realistic paradigms using Virtual Reality (VR) may be better suited to investigate authentic emotional states and their neuronal correlates. This preregistered study examines the neuronal underpinnings of naturalistic fear, measured using mobile electroencephalography (EEG). Seventy-five healthy participants entered a simulation in which they walked across a virtual plank which extended from the side of a skyscraper – either 80 stories up (the negative condition) or at street level (the neutral condition). Subjective ratings showed that the negative condition induced feelings of fear and presence. Following the VR experience, subjects passively viewed negative and neutral images from the International Affective Picture system (IAPS) outside of VR. We compared frontal alpha asymmetry between the plank and IAPS task and across valence of the conditions. Asymmetry indices (AI) in the plank task revealed greater right-hemispheric lateralization during the negative VR condition, relative to the neutral VR condition and to IAPS viewing. Within the IAPS task, no significant asymmetries were detected, though AIs in the VR task and in the IAPS task were negatively correlated suggesting that stronger right-hemispheric activation in the VR task was associated with stronger left-hemispheric activation during the IAPS task. In summary, our findings indicate that immersive technologies such as VR can advance emotion research by providing more ecologically valid ways to induce emotion.
Nicked tRNAs are stable reservoirs of tRNA halves in cells and biofluids

Nonvesicular extracellular RNAs (nv-exRNAs) constitute the majority of the extracellular RNAome, but little is known about their stability, function and potential use as disease biomarkers. Herein, we measured the stability of several naked RNAs when incubated in human serum, urine and cerebrospinal fluid (CSF). We identified extracellularly produced tRNA-derived small RNAs (tDRs) with half-lives of up to three hours in CSF. Contrary to widespread assumptions, these intrinsically stable small RNAs are full-length tRNAs containing broken phosphodiester bonds (i.e., nicked tRNAs). Standard molecular biology protocols, including phenol-based RNA extraction and heat, induce the artifactual denaturation of nicked tRNAs and the consequent in vitro production of tDRs. Broken bonds are roadblocks for reverse transcriptases, preventing amplification and/or sequencing of nicked tRNAs in their native state. To solve this, we performed enzymatic repair of nicked tRNAs purified under native conditions, harnessing the intrinsic activity of phage and bacterial tRNA repair systems. Enzymatic repair regenerated an RNase R-resistant tRNA-sized band in northern blot and enabled RT-PCR amplification of full-length tRNAs. We also separated nicked tRNAs from tDRs by chromatographic methods under native conditions, identifying nicked tRNAs inside stressed cells and in vesicle-depleted human biofluids. Dissociation of nicked tRNAs produces single-stranded tDRs that can be spontaneously taken up by human epithelial cells, positioning stable nv-exRNAs as potentially relevant players in intercellular communication pathways.
Profound lipid dysregulation in mutant TDP-43 mice is ameliorated by the glucocerebrosidase 2 inhibitor ambroxol

The importance of dyslipidemia in amyotrophic lateral sclerosis (ALS) patients is increasingly recognised as a potential key mechanism driving disease onset, progression and survival. Evidence in familial ALS models suggests that lipid composition is significantly affected, however clinically relevant models have yet to be investigated. Using a powerful lipidomic approach, we uncover significant dysregulation of glycosphingolipid (GSL) metabolism in both the spinal cord and skeletal muscles of transgenic TDP-43Q331K mice. Treatment with the selective glucocerebrosidase 2 (GBA2) inhibitor ambroxol at symptom onset significantly improved motor and gait functions in TDP-43Q331K mice. Ambroxol treatment preserved motor neurons and neuromuscular junctions which was associated with modulation of GSL metabolism. Our study establishes significant lipid dysregulation in a clinically relevant model of ALS. Importantly, we show positive therapeutic outcomes in a mouse model of TDP-43 proteinopathy, suggesting that ambroxol may be a promising candidate to treat underlying dyslipidemia and symptoms of ALS.
Neurogenin 2 and Neuronal Differentiation 1 Control Proper Development of the Chick Trigeminal Ganglion and Its Nerve Branches

The trigeminal ganglion contains the cell bodies of sensory neurons comprising cranial nerve V, which relays information related to pain, touch, and temperature from the face and head to the brain. Like other cranial ganglia, the trigeminal ganglion is composed of neuronal derivatives of two critical embryonic cell types, neural crest and placode cells. Neurogenesis within the cranial ganglia is promoted by Neurogenin 2 (Neurog2), which is expressed in trigeminal placode cells and their neuronal derivatives and transcriptionally activates neuronal differentiation genes like Neuronal Differentiation 1 (NeuroD1). Little is known, however, about the role of Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. To address this, we depleted Neurog2 and NeuroD1 from trigeminal placode cells with morpholinos and demonstrated that Neurog2 and NeuroD1 influence trigeminal ganglion development. While knockdown of both Neurog2 and NeuroD1 affected innervation of the eye, Neurog2 and NeuroD1 had opposite effects on ophthalmic nerve branch organization. Taken together, our results highlight, for the first time, functional roles for Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. These studies shed new light on the molecular mechanisms underlying trigeminal ganglion formation and may also provide insight into general cranial gangliogenesis and diseases of the peripheral nervous system.
Astrocytic TDP-43 dysregulation impairs memory by modulating antiviral pathways and interferon-inducible chemokines

TDP-43 pathology is prevalent in dementia but the cell type-specific effects of TDP-43 are not clear and therapeutic strategies to alleviate TDP-43-linked cognitive decline are lacking. We found that patients with Alzheimer’s disease (AD) or frontotemporal dementia (FTD) have aberrant TDP-43 accumulation in hippocampal astrocytes. In mouse models, induction of widespread or hippocampus-targeted accumulation in astrocytic TDP-43 caused progressive memory loss and localized changes in antiviral gene expression. These changes were cell-autonomous and correlated with impaired astrocytic defense against infectious viruses. Among the changes, astrocytes had elevated levels of interferon-inducible chemokines and neurons had elevated levels of the corresponding chemokine receptor CXCR3 in presynaptic terminals. CXCR3 stimulation altered presynaptic function and promoted neuronal hyperexcitability, akin to the effects of astrocytic TDP-43, and blockade of CXCR3 reduced this activity. Ablation of CXCR3 also prevented TDP-43-linked memory loss. Thus, astrocytic TDP-43 dysfunction contributes to cognitive impairment through aberrant chemokine-mediated astrocytic-neuronal interactions. Summary In dementia, protein buildup in glia enhances chemokine signaling to synapses and impairs specific aspects of neurocognitive function.
S175907872100129Xjra 989..994

A compact ultra-wideband (UWB) square and circular slot ground plane planar antenna with a modified circular patch for UWB communication is presented. This antenna has a low reflection coefficient and high gain in the range of 8.94 GHz, starting from 2.85 to 11.79 GHz. The proposed antenna demonstrates UWB behavior with electrically small dimensions of 0.18 λ0×0.14 λ0×0.015 λ0 (λ0 is the free-space wavelength at 2.85 GHz). The fractional bandwidth of the antenna is 122.1%, with stable radiations. The antenna’s maximum gain stands at 2.79 dBi, and the antenna’s peak efficiency stands at 72%, respectively. It is lightweight, compact, and easy to manufacture. Hence, it can be used for the complete range of UWB applications and covers Wi-Max/WLAN/ X-Band and Ku-Band.