Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-cost, handheld near-infrared spectroscopy for root dry matter content prediction in cassava

Over 800 million people across the tropics rely on cassava as a major source of calories. While the root dry matter content (RDMC) of this starchy root crop is important for both producers and consumers, characterization of RDMC by traditional methods is time-consuming and laborious for breeding programs. Alternate phenotyping methods have been proposed but lack the accuracy, cost, or speed ultimately needed for cassava breeding programs. For this reason, we investigated the use of a low-cost, handheld NIR spectrometer for field-based RDMC prediction in cassava. Oven-dried measurements of RDMC were paired with 21,044 scans of roots of 376 diverse clones from 10 field trials in Nigeria and grouped into training and test sets based on cross-validation schemes relevant to plant breeding programs. Mean partial least squares regression model performance ranged from R2p = 0.62 - 0.89 for within-trial predictions, which is within the range achieved with laboratory-grade spectrometers in previous studies. Relative to other factors, model performance was highly impacted by the inclusion of samples from the same environment in both the training and test sets. Random forest variable importance analysis of root spectra revealed increased importance in a region previously identified as predictive of water content in plants (~950 - 990 nm). With appropriate model calibration, the tested spectrometer will allow for field-based collection of spectral data with a smartphone for accurate RDMC prediction and potentially other quality traits, a step that could be easily integrated into existing harvesting workflows of cassava breeding programs. CORE IDEAS A low-cost, handheld near-infrared spectrometer was tested for phenotyping of cassava roots Plant breeding-relevant cross-validation schemes were used for predictions High prediction accuracies were achieved for cassava root dry matter content A spectral region predictive of plant water content was identified as important
Genomic sequences and RNA binding proteins predict RNA splicing kinetics in various single-cell contexts

RNA splicing is a key step of gene expression in higher organisms. Accurate quantification of the two-step splicing kinetics is of high interests not only for understanding the regulatory machinery, but also for estimating the RNA velocity in single cells. However, the kinetic rates remain poorly understood due to the intrinsic low content of unspliced RNAs and its stochasticity across contexts. Here, we estimated the relative splicing efficiency across a variety of single-cell RNA-Seq data with scVelo. We further extracted three large feature sets including 92 basic genomic sequence features, 65,536 octamers and 120 RNA binding proteins features and found they are highly predictive to RNA splicing efficiency across multiple tissues on human and mouse. A set of important features have been identified with strong regulatory potentials on splicing efficiency. This predictive power brings promise to reveal the complexity of RNA processing and to enhance the estimation of single-cell RNA velocity.
H3K27 Acetylated Nucleosomes Facilitate HMGN Protein Localization at Regulatory Sites to Modulate The Interaction of Transcription Factors with Chromatin

Nucleosomes containing acetylated H3K27 are a major epigenetic mark of active chromatin and identify cell-type specific chromatin regulatory regions which serve as binding sites for transcription factors. Here we show that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 bind preferentially to H3K27ac nucleosomes at cell-type specific chromatin regulatory regions. HMGNs bind directly to the acetylated nucleosome; the H3K27ac residue and linker DNA facilitate the preferential binding of HMGNs to the modified nucleosomes. Loss of HMGNs increases the levels of H3K27me3 and the histone H1 occupancy at enhancers and promoters and alters the interaction of transcription factors with chromatin. These experiments indicate that the H3K27ac epigenetic mark affects the interaction of architectural protein with chromatin regulatory sites and provide insights into the molecular mechanism whereby ubiquitous chromatin binding proteins, which bind to chromatin without DNA sequence specificity, localize to regulatory chromatin and modulate cell-type specific gene expression.
Neural dynamics between anterior insular cortex and right supramarginal gyrus dissociate genuine affect sharing from automatic responses to pretended pain

Empathy for pain engages both shared affective responses and self-other distinction. In this study, we addressed the highly debated question of whether neural responses previously linked to affect sharing could result from the perception of salient affective displays. Moreover, we investigated how affect sharing and self-other distinction interact to determine our response to a pain that is either perceived as genuine or pretended (while in fact both were acted for reasons of experimental control). We found stronger activations in regions associated with affect sharing (anterior insula, aIns, and anterior mid-cingulate cortex, aMCC) as well as with affective self-other distinction (right supramarginal gyrus, rSMG), in participants watching video clips of genuine vs. pretended facial expressions of pain. Using dynamic causal modeling (DCM), we then assessed the neural dynamics between the right aIns and rSMG in these two conditions. This revealed a reduced inhibitory effect on the aIns to rSMG connection for genuine compared to pretended pain. For genuine pain only, brain-to-behavior regression analyses highlighted a linkage between this inhibitory effect on the one hand, and pain ratings as well as empathic traits on the other. These findings imply that if the pain of others is genuine and thus calls for an appropriate empathic response, neural responses in the aIns indeed seem related to affect sharing and self-other distinction is engaged to avoid empathic over-arousal. In contrast, if others merely pretend to be in pain, the perceptual salience of their painful expression results in neural responses that are down-regulated to avoid inappropriate affect sharing and social support.
Neural correlates of audio-visual integration of socially meaningful information in macaque monkeys

Social interactions rely on the ability to interpret semantic and emotional information, often from multiple sensory modalities. In human and nonhuman primates, both the auditory and visual modalities are used to generate and interpret communicative signals. In individuals with autism, not only are there deficits in social communication, but in the integration of audio-visual information. At present, we know little about the neural mechanisms that subserve the interpretation of complex social events, including the audio-visual integration that is often required with accompanying communicative signals. Based on heart rate estimates and fMRI in two macaque monkeys (Macaca mulatta), we show that individuals systematically associate affiliative facial expressions or social scenes with corresponding affiliative vocalizations, aggressive facial expressions or social scenes with corresponding aggressive vocalizations and escape visual scenes with scream vocalizations. In contrast, vocalizations that are incompatible with the visual information are fully suppressed, suggesting top-down regulation over the processing of sensory input. The process of binding audio-visual semantic and contextual information relies on a core functional network involving the superior temporal sulcus (STS) and lateral sulcus (LS). Peak activations in both sulci co-localize with face or voice patches that have been previously described. While all of these regions of interest (ROIs) respond to both auditory and visual information, LS ROIs have a preference for auditory and audio-visual congruent stimuli while STS ROIs equally respond to auditory, visual and audio-visual congruent stimuli. To further specify the cortical network involved in the control of this semantic association, we performed a whole brain gPPI functional connectivity analysis on the LS and STS cumulated ROIs. This gPPI analysis highlights a functional network connected to the LS and STS, involving the anterior cingulate cortex (ACC), area 46 in the dorsolateral prefrontal cortex (DLPFC), the orbitofrontal cortex (OFC), the intraparietal sulcus (IPS), the insular cortex and subcortically, the amygdala and the hippocampus. Comparing human and macaque results, we propose that the integration of audio-visual information for congruent, meaningful social events involves homologous neural circuitry, specifically, an emotional network composed of the STS, LS, ACC, OFC, and limbic areas, including the amygdala, and an attentional network including the STS, LS, IPS and DLPFC. As such, these networks are critical to the amodal representation of social meaning, thereby providing an explanation for some of deficits observed in autism.
Neuronal genetic rescue normalizes brain network dynamics in a lysosomal storage disorder despite persistent storage accumulation

Although neurologic symptoms occur in two-thirds of lysosomal storage disorders (LSDs), for most we do not understand the mechanisms underlying brain dysfunction. A major unanswered question is if the pathogenic hallmark of LSDs, storage accumulation, induces functional defects directly or is a disease bystander. Also, for most LSDs we do not know the impact of loss-of-function in individual cell types. Understanding these critical questions are essential to therapy development. Here, we determined the impact of genetic rescue in distinct cell types on neural circuit dysfunction in CLN3 disease, the most common pediatric dementia and a representative LSD. We restored Cln3 expression via AAV-mediated gene delivery and conditional genetic rescue in a CLN3 mouse model. Surprisingly, we found that low-level rescue of Cln3 expression in neurons alone normalized clinically-relevant electrophysiologic markers of network dysfunction, despite the presence of substantial residual histopathology, in contrast to restoring expression in astrocytes. Thus, loss of Cln3 function in neurons, not storage accumulation, underlies neurologic dysfunction in CLN3 disease, implying that storage clearance may be an inappropriate target for therapy development and an ineffectual biomarker.
Simple and efficient heterologous expression of necrosis-inducing effectors using the model plant Nicotiana benthamiana

Plant fungal pathogens cause devastating diseases on cereal plants and threaten global food security. During infection, these pathogens secrete proteinaceous effectors that promote disease. Some of these effectors from necrotrophic plant pathogens induce a cell death response (necrosis), which facilitates pathogen growth in planta. Characterisation of these effectors typically requires heterologous expression and microbial expression systems such as bacteria and yeast are the predominantly used. However, microbial expression systems often require optimization for any given effector and are, in general, not suitable for effectors involving cysteine bridges and posttranslational modifications for activity. Here, we describe a simple and efficient method for expressing such effectors in the model plant Nicotiana benthamiana. Briefly, an effector protein is transiently expressed and secreted into the apoplast of N. benthamiana by Agrobacterium-mediated infiltration. Two-to-three days subsequent to agroinfiltration, the apoplast from the infiltrated leaves is extracted and can be directly used for phenotyping on host plants. The efficacy of this approach was demonstrated by expressing the ToxA, Tox3 and Tox1 necrosis-inducing effectors from Parastagonospora nodorum. All three effectors produced in N. benthamiana were capable of inducing necrosis in wheat lines, and two of three showed visible bands on Coomassie-stained gel. These data suggest that N. benthamiana-agroinfiltration system is a feasible tool to obtain fungal effectors, especially those that require disulfide bonds and posttranslational modifications. Furthermore, due to the low number of proteins typically observed in the apoplast (compared to intracellular), this simple and high-throughput approach circumvents the requirement to lyse cells and further purify the target proteins that is required in other heterologous systems. Because of its simplicity and potential for high-throughput, this method is highly amenable to the phenotyping of candidate protein effectors on host plants.
Do additional, visual elements in recorded lectures influence the processing of subtitles?

Abstract Given the recent and sudden transition from classrooms to online teaching during the Covid-19 pandemic, more emphasis is being placed on providing the same classroom experience to students on an online (or e-learning) platform. To increase accessibility to online content, subtitles are sometimes added to videos, but this may come at a cost. Not only is the addition of subtitles an extra source of information to be processed, the type of subtitle may differ (automatic or standardised) and subtitles are in competition with other sources of information that also need to be processed. This can result in subtitles becoming redundant, failing to contribute to accessibility at all. This study was conducted to determine how the processing of subtitles was influenced by redundant information (graphs, tables, etc.) on the screen, using eye-tracking data. Two different types of subtitles, automatic and standardised, were also used. Findings indicated that the standardised subtitles were 45% more likely to be processed than the automatic subtitles and that both types of subtitles were 24% less likely to be processed with redundant information. The findings suggest that great care needs to be taken when adding subtitles to videos and how these videos are structured.
SARS-CoV-2 Bearing a Mutation at the S1/S2 Cleavage Site Exhibits Attenuated Virulence and Confers Protective Immunity

SARS-CoV-2 uses its spike protein to enter target cells. The spike protein is cleaved by a host protease, and this event facilitates viral entry and broadens cell tropism. ABSTRACT Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) possesses a discriminative polybasic cleavage motif in its spike protein that is recognized by the host furin protease. Proteolytic cleavage activates the spike protein, thereby affecting both the cellular entry pathway and cell tropism of SARS-CoV-2. Here, we investigated the impact of the furin cleavage site on viral growth and pathogenesis using a hamster animal model infected with SARS-CoV-2 variants bearing mutations at the furin cleavage site (S gene mutants). In the airway tissues of hamsters, the S gene mutants exhibited low growth properties. In contrast to parental pathogenic SARS-CoV-2, hamsters infected with the S gene mutants showed no body weight loss and only a mild inflammatory response, thereby indicating the attenuated variant nature of S gene mutants. This transient infection was sufficient for inducing protective neutralizing antibodies that cross-react with different SARS-CoV-2 lineages. Consequently, hamsters inoculated with S gene mutants showed resistance to subsequent infection with both the parental strain and the currently emerging SARS-CoV-2 variants belonging to lineages B.1. 1.7 and P.1. Taken together, our findings revealed that the loss of the furin cleavage site causes attenuation in the airway tissues of hamsters and highlighted the potential benefits of S gene mutants as potential immunogens. IMPORTANCE SARS-CoV-2 uses its spike protein to enter target cells. The spike protein is cleaved by a host protease, and this event facilitates viral entry and broadens cell tropism. In this study, we employed SARS-CoV-2 mutants lacking the S protein cleavage site and characterized their growth and pathogenicity using hamsters, a laboratory animal model for SARS-CoV-2 infection. These mutants exerted low pathogenicity but induced sufficient levels of neutralizing antibodies in hamsters, which protected hamsters from rechallenge with pathogenic clinical SARS-CoV-2 strains. These virus mutants may be used as protective immunogens against SARS-CoV-2 infection.
Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique

Pseudouridine (Ψ) is the most common non-canonical ribonucleoside present on mammalian non-coding RNAs (ncRNAs), including rRNAs, tRNAs and snRNAs, where it contributes ∼7% of the total uridine level. However, Ψ constitutes only ∼0.1% of the uridines present on mRNAs and its effect on mRNA function remains unclear. Ψ residues have been shown to inhibit the detection of exogenous RNA transcripts by host innate immune factors, thus raising the possibility that viruses might have subverted the addition of Ψ residues to mRNAs by host pseudouridine synthase (PUS) enzymes as a way to inhibit antiviral responses in infected cells. Here, we describe and validate a novel antibody-based Ψ mapping technique called photo-crosslinking assisted Ψ sequencing (PA-Ψ-seq) and use it to map Ψ residues on not only multiple cellular RNAs but also on the mRNAs and genomic RNA encoded by HIV-1. We describe several 293T-derived cell lines in which human PUS enzymes previously reported to add Ψ residues to human mRNAs, specifically PUS1, PUS7 and TRUB1/PUS4, were inactivated by gene editing. Surprisingly, while this allowed us to assign several sites of Ψ addition on cellular mRNAs to each of these three PUS enzymes, the Ψ sites present on HIV-1 transcripts remained unaffected. Moreover, loss of PUS1, PUS7 or TRUB1 function did not significantly reduce the level of Ψ residues detected on total human mRNA below the ∼0.1% level seen in wild type cells, thus implying that the PUS enzyme(s) that adds the bulk of Ψ residues to human mRNAs remains to be defined.
How marine currents and environment shape plankton genomic differentiation: a mosaic view from Tara Oceans metagenomic data

Plankton seascape genomics show different trends from large-scale weak differentiation to micro-scale structures. Prior studies underlined the influence of environment and seascape on a few single species differentiation and adaptation. However, these works generally focused on few single species, sparse molecular markers, or local scales. Here, we investigate the genomic differentiation of plankton at macro-scale in a holistic approach using Tara Oceans metagenomic data together with a reference-free computational method to reconstruct the FST-based genomic differentiation of 113 marine planktonic species using metavariant species (MVS). These MVSs, modelling the species only by their polymorphism, include a wide range of taxonomic groups comprising notably 46 Maxillopoda/Copepoda, 24 Bacteria, 5 Dinoflagellates, 4 Haptophytes, 3 Cnidarians, 3 Mamiellales, 2 Ciliates, 1 Collodaria, 1 Echinoidea, 1 Pelagomonadaceae, 1 Cryptophyta and 1 Virus. The analyses showed that differentiation between populations was significantly lower within basins and higher in bacteria and unicellular eukaryotes compared to zooplantkon. By partitioning the variance of pairwise-FSTmatrices, we found that the main drivers of genomic differentiation were Lagrangian travel time, salinity and temperature. Furthermore, we classified MVSs into parameter-driven groups and showed that taxonomy poorly determines which environmental factor drives genomic differentiation. This holistic approach of plankton genomic differentiation for large geographic scales, a wide range of taxa and different oceanic basins, offers a systematic framework to analyse population genomics of non-model and undocumented marine organisms.
Metagenomic investigation of the equine faecal microbiome reveals extensive taxonomic and functional diversity

Background The horse plays crucial roles across the globe, including in horseracing, as a working and companion animal and as a food animal. The horse hindgut microbiome makes a key contribution in turning a high fiber diet into body mass and horsepower. However, despite its importance, the horse hindgut microbiome remains largely undefined. Here, we applied culture-independent shotgun metagenomics to thoroughbred equine faecal samples to deliver novel insights into this complex microbial community. Results We performed metagenomic sequencing on five equine faecal samples to construct 123 high- or medium-quality metagenome-assembled genomes from Bacteria and Archaea. In addition, we recovered nearly 200 bacteriophage genomes. We document surprising taxonomic and functional diversity, encompassing dozens of novel or unnamed bacterial genera and species, to which we have assigned new Candidatus names. Many of these genera are conserved across a range of mammalian gut microbiomes. Conclusions Our metagenomic analyses provide new insights into the bacterial, archaeal and bacteriophage components of the horse gut microbiome. The resulting datasets provide a key resource for future high-resolution taxonomic and functional studies on the equine gut microbiome.
Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever, for which there are limited treatment options. Successful LASV entry requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of GP1 mutant proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus residue (L84N, K88E, L10F, and H170S) reduced the binding affinity of GP1LASV for LAMP1. Moreover, all the mutations caused decreases in GPC-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, whereas L107F and H170S had only mild effects on infectivity. Notably, in LAMP1 knockout cells, all four mutants showed reduced pseudovirus infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order L84N > L107F > K88E > H170S. IMPORTANCE Lassa virus requires pH-dependent receptor switch to infect host cells; however, the underlying molecular mechanisms of this process are not well known. Here, we identify four residues, L84, K88, L107, and H170 that contribute to the interaction with the second receptor lysosome-associated membrane protein 1 (LAMP1). Mutant any of the four residues would impair the binding affinity to LAMP1, decrease the glycoprotein mediated membrane fusion, and reduce the pseudovirus infectivity.