Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis and characterization of Fe(III)-Fe(II)-Mg-Al smectite solid solutions and implications for planetary science

Abstract This study demonstrates the synergies and limits of multiple measurement types for the detection of smectite chemistry and oxidation state on planetary surfaces to infer past geochemical conditions. Smectite clay minerals are common products of water-rock interactions throughout the solar system, and their detection and characterization provides important clues about geochemical conditions and past environments if sufficient information about their composition can be discerned. Here, we synthesize and report on the spectroscopic properties of a suite of smectite samples that span the intermediate compositional range between Fe(II), Fe(III), Mg, and Al end-member species using bulk chemical analyses, X‑ray diffraction, Vis/IR reflectance spectroscopy, UV and green-laser Raman spectroscopy, and Mössbauer spectroscopy. Our data show that smectite composition and the oxidation state of octahedral Fe can be reliably identified in the near infrared on the basis of combination and fundamental metal-OH stretching modes between 2.1–2.9 μm, which vary systematically with chemistry. Smectites dominated by Mg or Fe(III) have spectrally distinct fundamental and combination stretches, whereas Al-rich and Fe(II)-rich smectites have similar fundamental minima near 2.76 μm, but have distinct combination M-OH features between 2.24 and 2.36 μm. We show that with expanded spectral libraries that include intermediate composition smectites and both Fe(III) and Fe(II) oxidation states, more refined characterization of smectites from MIR data is now possible, as the position of the 450 cm–1 absorption shifts systematically with octahedral Fe content, although detailed analysis is best accomplished in concert with other characterization methods. Our data also provide the first Raman spectral libraries of smectite clays as a function of chemistry, and we demonstrate that Raman spectroscopy at multiple excitation wavelengths can qualitatively distinguish smectite clays of different structures and can enhance interpretation by other types of analyses. Our sample set demonstrates how X‑ray diffraction can distinguish between dioctahedral and trioctahedral smectites using either the (02,11) or (06,33) peaks, but auxiliary information about chemistry and oxidation state aids in specific identifications. Finally, the temperature-dependent isomer shift and quadrupole splitting in Mössbauer data are insensitive to changes in Fe content but reliability differentiates Fe within the smectite mineral structure.
SARS-CoV-2 Nsp14 activates NF-κB signaling and induces IL-8 upregulation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-κB activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-κB signaling. Nsp14 caused the nuclear translocation of NF-κB p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation was further confirmed in lung tissue samples from COVID-19 patients. A previous proteomic screen identified the putative interaction of Nsp14 with host Inosine-5’-monophosphate dehydrogenase 2 (IMPDH2) protein, which is known to regulate NF-κB signaling. We confirmed the Nsp14-IMPDH2 protein interaction and found that IMPDH2 knockdown or chemical inhibition using ribavirin (RIB) and mycophenolic acid (MPA) abolishes Nsp14-mediated NF-κB activation and cytokine induction. Furthermore, IMDPH2 inhibitors (RIB, MPA) efficiently blocked SARS-CoV-2 infection, indicating that IMDPH2, and possibly NF-κB signaling, is beneficial to viral replication. Overall, our results identify a novel role of SARS-CoV-2 Nsp14 in causing the activation of NF-κB.
A neural network account of memory replay and knowledge consolidation

Replay can consolidate memories through offline neural reactivation related to past experiences. Category knowledge is learned across multiple experiences, and its subsequent generalisation is promoted by consolidation and replay during rest and sleep. However, aspects of replay are difficult to determine from neuroimaging studies. We provided insights into category knowledge replay by simulating these processes in a neural network which approximated the roles of the human ventral visual stream and hippocampus. Generative replay, akin to imagining new category instances, facilitated generalisation to new experiences. Consolidation-related replay may therefore help to prepare us for the future as much as remember the past. Generative replay was more effective in later network layers functionally similar to the lateral occipital cortex than layers corresponding to early visual cortex, drawing a distinction between neural replay and its relevance to consolidation. Category replay was most beneficial for newly acquired knowledge, suggesting replay helps us adapt to changes in our environment. Finally, we present a novel mechanism for the observation that the brain selectively consolidates weaker information; a reinforcement learning process in which categories were replayed according to their contribution to network performance. This reinforces the idea of consolidation-related replay as an active rather than passive process.
Alpha phase-amplitude tradeoffs predict visual perception

Spontaneous alpha oscillations (~10 Hz) have been associated with various cognitive functions, including perception. Their phase and amplitude independently predict cortical excitability and subsequent perceptual performance. Yet, the causal role of alpha phase-amplitude tradeoffs on visual perception remains ill-defined. We aimed to fill this gap and tested two clear predictions from the Pulsed Inhibition theory according to which alpha oscillations are associated with periodic functional inhibition. (1) High alpha amplitude induces cortical inhibition at specific phases, associated with low perceptual performance, while at opposite phases, inhibition decreases (potentially increasing excitation) and perceptual performance increases. (2) Low alpha amplitude is less susceptible to these phasic (periodic) pulses of inhibition, leading to overall higher perceptual performance. Here, cortical excitability was assessed in humans using phosphene (illusory) perception induced by single pulses of transcranial magnetic stimulation (TMS) applied over visual cortex at perceptual threshold, and its post-pulse evoked activity recorded with simultaneous electroencephalography (EEG). We observed that pre-pulse alpha phase modulates the probability to perceive a phosphene, predominantly for high alpha amplitude, with a non-optimal phase for phosphene perception between −π/2 and −π/4. The pre-pulse non-optimal phase further leads to an increase in post-pulse evoked activity (ERP), in phosphene-perceived trials specifically. Together, these results show that alpha oscillations create periodic inhibitory moments when alpha amplitude is high, leading to periodic decrease of perceptual performance. This study provides strong causal evidence in favor of the Pulsed Inhibition theory. Visual Abstract Significance Statement The Pulsed Inhibition theory predicts that the functional inhibition induced by high alpha oscillations’ amplitude is periodic, with specific phases decreasing neural firing and perceptual performance. In turn, low alpha oscillations’ amplitude is less susceptible to phasic moments of pulsed inhibition leading to overall higher perceptual performance. Using TMS with simultaneous EEG recordings in humans, we found that specific phases of spontaneous alpha oscillations (~10 Hz) decrease cortical excitability and the subsequent perceptual outcomes predominantly when alpha amplitude is high. Our results provide strong causal evidence in favor of the Pulsed Inhibition theory.
Membrane architecture and adherens junctions contribute to strong Notch pathway activation

The Notch pathway mediates cell-to-cell communication in a variety of tissues, developmental stages and organisms. Pathway activation relies on the interaction between transmembrane ligands and receptors on adjacent cells. As such, pathway activity could be influenced by the size, composition or dynamics of contacts between membranes. The initiation of Notch signalling in the Drosophila embryo occurs during cellularization, when lateral cell membranes and adherens junctions are first being deposited, allowing us to investigate the importance of membrane architecture and specific junctional domains for signaling. By measuring Notch dependent transcription in live embryos we established that it initiates while lateral membranes are growing and that signalling onset correlates with a specific phase in their formation. However, the length of the lateral membranes per se was not limiting. Rather, the adherens junctions, which assemble concurrently with membrane deposition, contributed to the high levels of signalling required for transcription, as indicated by the consequences from depleting α-Catenin. Together, these results demonstrate that the establishment of lateral membrane contacts can be limiting for Notch trans-activation and suggest that adherens junctions play an important role in modulating Notch activity.
Impaired function and delayed regeneration of dendritic cells in COVID-19

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DC) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute disease to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage- HLADR+ cells lacking DC markers. Increased frequency of the recently discovered CD163+ CD14+ DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of PD-L1 in conventional DC (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.
Pollinator habitat plantings benefit wild, native bees, but do not necessarily favor rare species

Installing pollinator habitat is a ubiquitous conservation tool, but little is known about which pollinator taxa require support, or which benefit from habitat installations. We studied the response of rare and common bees to pollinator habitat enhancement. We used independent regional datasets to designate bee species as common or rare based on their rank according to one of three metrics: a) site occurrence frequency, b) local relative abundance, and c) geographic range size. We asked whether the abundance or richness of rare and common bees were greater in pollinator habitat, relative to old-field controls. Because we used an arbitrary, quantile-based cutoff to categorize species rarity, we conducted sensitivity analysis and controlled for rarity classification errors with a null model. With this null model, we determined whether rare and/or common species responded to pollinator habitat disproportionately, compared to the expectation for ‘typical’ bee species. We found that the number of individuals and of species designated as rare based on local relative abundance was greater in pollinator habitat enhancements. The number of individuals from bee species designated as rare based on site occurrence was lower in pollinator habitat enhancements, but the number of species was not clearly different between habitat types. We did not find a clear positive nor negative effect of habitat enhancement for species designated rare based on geographic range size. For all three rarity metrics, common species increased in abundance and richness in pollinator habitat relative to controls. Null models indicated that in most cases, neither rare nor common species disproportionately benefited from pollinator habitat. Synthesis and Applications: Our results suggest that pollinator habitat can lead to an increase in the abundance and richness of bees, including species that are rare and that are common. However, rare species appeared to respond differently than typical species, and depending on how species were classified as rare, could display muted or even negative responses to habitat enhancement. Targeting rare species with specific floral resources or unique habitat types may lead to better outcomes for rare and threatened species.
APOE4 expression confers a mild, persistent reduction in neurovascular function in the visual cortex and hippocampus of awake mice

Young mice possessing the e4 allele of the Apolipoprotein (APOE) gene (a risk factor for Alzheimer’s disease (AD)) have previously been shown to have dramatic decreases in vascular function, suggesting APOE4 may confer its risk via the vasculature. However, in human carriers, vascular and cognitive function decrease later in life. Mouse data may be confounded by an increased impact of anaesthesia and surgery in APOE4 animals, and has also focused on sensory cortices, ignoring medial lobe structures more sensitive to AD. To clarify how APOE4 expression alters neurovascular function, we studied the visual cortex and hippocampus of awake APOE3 and APOE4 targeted replacement mice, using 2-photon microscopy of neurons and blood vessels. We found milder vascular deficits than studies using anaesthetised preparations: functional hyperaemia was unaffected in APOE4 mice and neuronal or vascular function did not decrease with age. Instead, vascular responsiveness was lower at all ages, arteriole vasomotion was reduced and neuronal calcium signals during visual stimulation were increased. This suggests that, independently, APOE4 expression is not catastrophic but alters neurovascular physiology towards a state more sensitive to insults such as surgery or beta amyloid accumulation. Understanding how APOE4 expression interacts with these insults will be critical for understanding the emergence of AD in APOE4 carriers.
Epigenetic Patterns in a Complete Human Genome

The completion of the first telomere-to-telomere human genome, T2T-CHM13, enables exploration of the full epigenome, removing limitations previously imposed by the missing reference sequence. Existing epigenetic studies omit unassembled and unmappable genomic regions (e.g. centromeres, pericentromeres, acrocentric chromosome arms, subtelomeres, segmental duplications, tandem repeats). Leveraging the new assembly, we were able to measure enrichment of epigenetic marks with short reads using k-mer assisted mapping methods. This granted array-level enrichment information to characterize the epigenetic regulation of these satellite repeats. Using nanopore sequencing data, we generated base level maps of the most complete human methylome ever produced. We examined methylation patterns in satellite DNA and revealed organized patterns of methylation along individual molecules. When exploring the centromeric epigenome, we discovered a distinctive dip in centromere methylation consistent with active sites of kinetochore assembly. Through long-read chromatin accessibility measurements (nanoNOMe) paired to CUT&RUN data, we found the hypomethylated region was extremely inaccessible and paired to CENP-A/B binding. With long-reads we interrogated allele-specific, longrange epigenetic patterns in complex macro-satellite arrays such as those involved in X chromosome inactivation. Using the single molecule measurements we can clustered reads based on methylation status alone distinguishing epigenetically heterogeneous and homogeneous areas. The analysis provides a framework to investigate the most elusive regions of the human genome, applying both long and short-read technology to grant new insights into epigenetic regulation.
MK2a inhibitor CMPD1 abrogates chikungunya virus infection by modulating actin remodeling pathway

Chikungunya virus (CHIKV) epidemics around the world have created public health concern with the unavailability of effective drugs and vaccines. This emphasizes the need for molecular understanding of host-virus interactions for developing effective targeted antivirals. Microarray analysis was carried out using CHIKV strain (Prototype and Indian) infected Vero cells and two host isozymes, MK2 and MK3 were selected for further analysis. Gene silencing and drug treatment were performed in vitro and in vivo to unravel the role of MK2/MK3 in CHIKV infection. Gene silencing of MK2 and MK3 abrogated around 58% CHIKV progeny release from the host cell and a MK2 activation (a) inhibitor (CMPD1) treatment demonstrated 68% inhibition of viral infection suggesting a major role of MAPKAPKs during the late phase of CHIKV infection in vitro. Further, it was observed that the inhibition in viral infection is primarily due to the abrogation of lamellipodium formation through modulation of factors involved in the actin cytoskeleton remodeling pathway that is responsible for releasing the virus from the infected cells. Moreover, CHIKV-infected C57BL/6 mice demonstrated reduction in the viral copy number, lessened disease score and better survivability after CMPD1 treatment. In addition, reduction in expression of key pro-inflammatory mediators such as CXCL13, RAGE, FGF, MMP9 and increase in HGF (a CHIKV infection recovery marker) was observed indicating the effectiveness of this drug against CHIKV. Additionally, CMPD1 also inhibited HSV1 and SARS CoV2-19 infection in vitro. Taken together it can be proposed that MK2 and MK3 are crucial host factors for CHIKV infection and can be considered as key targets for developing effective anti-CHIKV strategies in future. Author summary Chikungunya virus has been a dreaded disease from the first time it occurred in 1952 Tanzania. Since then it has been affecting the different parts of the world at different time periods in large scale. It is typically transmitted to humans by bites of Aedes aegypti and Aedes albopictus mosquitoes. Although, studies have been undertaken to combat the disease still there are no effective strategies like vaccines or antivirals against it. Therefore it is essential to understand the virus and host interaction to overcome this hurdle. In this study two host factors MK2 and MK3 have been taken into consideration to see how they regulate the multiplication of the virus. The in vitro experiments demonstrated that inhibition of MK2 and MK3 restricted viral infection Further, it was observed that this is due to the blocking of lamellipodium formation by modifying the factors involved in the actin cytoskeleton remodeling pathway that is responsible for releasing the virus from the infected cells. Besides, decreased disease score as well as better survivability was noticed in the in vivo experiments with mice. Therefore, MK2 and MK3 could be considered as the key targets for controlling CHIKV infection.
Parthenogenesis and the Evolution of Anisogamy

Recently, it was pointed out [1] that classic models for the evolution of anisogamy do not take into account the possibility of parthenogenetic reproduction, even though sex is facultative in many relevant taxa (e.g. algae) that harbour both anisogamous and isogamous species. Here we complement the analysis of [1] with an approach where we assume that the relationship between progeny size and its survival may differ between parthenogenetically and sexually produced progeny, favouring either the former or the latter. We show that the findings of [1], that parthenogenesis can stabilise isogamy relative to the obligate sex case, extend to our scenarios. We additionally investigate two different ways for one mating type to take over the entire population. First, parthenogenesis can lead to biased sex ratios that are sufficiently extreme that one type can displace the other, leading to de facto asexuality for the remaining type that now lacks partners to fuse with. This process involves positive feedback: microgametes, being numerous, lack opportunities for syngamy, and should they proliferate parthenogenetically, the next generation makes this asexual route even more prominent for microgametes. Second, we consider mutations to strict asexuality in producers of micro- or macrogametes, and show that the prospects of asexual invasion depend strongly on the mating type in which the mutation arises. Perhaps most interestingly, we also find scenarios in which parthenogens have an intrinsic survival advantage yet facultatively sexual isogamous populations are robust to the invasion of asexuals, despite us assuming no genetic benefits of recombination. Here equal contribution from both mating types to zygotes that are sufficiently well provisioned can outweigh the additional costs associated with syngamy.
Convolutional neural networks trained with a developmental sequence of blurry to clear images reveal core differences between face and object processing

Although convolutional neural networks (CNNs) provide a promising model for understanding human vision, most CNNs lack robustness to challenging viewing conditions such as image blur, whereas human vision is much more reliable. Might robustness to blur be attributable to vision during infancy, given that acuity is initially poor but improves considerably over the first several months of life? Here, we evaluated the potential consequences of such early experiences by training CNN models on face and object recognition tasks while gradually reducing the amount of blur applied to the training images. For CNNs trained on blurry to clear faces, we observed sustained robustness to blur, consistent with a recent report by Vogelsang and colleagues (2018). By contrast, CNNs trained with blurry to clear objects failed to retain robustness to blur. Further analyses revealed that the spatial frequency tuning of the two CNNs was profoundly different. The blurry to clear face-trained network successfully retained a preference for low spatial frequencies, whereas the blurry to clear object-trained CNN exhibited a progressive shift toward higher spatial frequencies. Our findings provide novel computational evidence showing how face recognition, unlike object recognition, allows for more holistic processing. Moreover, our results suggest that blurry vision during infancy is insufficient to account for the robustness of adult vision to blurry objects.