Miracle-dz/UniFAR-FTUs huggingface dataset:
Root architecture plasticity in response to endoparasitic cyst nematodes is mediated by damage signaling

Plant root architecture plasticity in response to biotic stresses has not been thoroughly investigated. Infection by the endoparasitic cyst nematodes induces root architectural changes that involve the formation of secondary roots at infection sites. However, the molecular mechanisms regulating secondary root formation in response to cyst nematode infection remain largely unknown. We first assessed whether secondary roots form in a nematode-density dependent manner by challenging wild type Arabidopsis plants with increasing numbers of cyst nematodes (Heterodera schachtii). Next, by using jasmonate-related reporter lines and knock-out mutants, we tested if tissue damage by nematodes triggers secondary root formation. Finally, we verified whether damage-induced secondary root formation depends on local auxin biosynthesis at nematode infection sites. Intracellular host invasion by H. schachtii triggers a transient local increase in jasmonates, which activates the expression of ERF109 in a COI1-dependent manner. Knock-out mutations in COI1 and ERF109 disrupt the nematode-density dependent increase of secondary roots observed in wildtype plants. Furthermore, ERF109 regulates secondary root formation upon H. schachtii infection via local auxin biosynthesis. Host invasion by H. schachtii triggers secondary root formation via the damage-induced jasmonate-dependent ERF109 pathway. This points at a novel mechanism underlying plant root plasticity in response to biotic stress.
Optical Modulation of Blood-Brain-Tumor Barrier Permeability Enhances Drug Delivery in Diverse Preclinical Glioblastoma Models

Glioblastoma multiforme (GBM) is the most prevalent malignant tumor in the central nervous system. It has diverse phenotypes, including diffuse single-cell infiltration in which the tumor cells co-opt the normal microvasculature, and the neovascularization of an expanding tumor mass. The blood-brain-tumor barrier (BBTB) is a significant obstacle to GBM treatment and restricts entry of most FDA-approved effective oncology drugs. Herein, we report that picosecond laser excitation of vascular-targeted plasmonic gold nanoparticles (AuNPs) can non-invasively and reversibly modulate the BBTB permeability (optoBBTB). OptoBBTB enhances the delivery of paclitaxel (Taxol) in two genetically engineered glioma models (GEMM) that span the spectrum of GBM phenotypes. OptoBBTB followed by Taxol delivery effectively suppresses tumor growth and prolongs the survival time of both GEMM. Moreover, our results raise the possibility that paclitaxel, which is amongst the most widely used oncology drugs because of its proven efficacy but has been abandoned for GBM following its failure to efficacy in early phase clinical trials due to poor blood-brain barrier (BBB) penetration, could now be reconsidered in combination with strategies to increase BBB permeability. In summary, optoBBTB is a novel and effective approach to increase the delivery of therapeutics with limited BBB permeability to treat neoplastic and non-neoplastic brain diseases.
Feedforward attentional selection in sensory cortex

Salient objects stand out (pop-out) from their surroundings, grabbing our attention. Whether this phenomenon is a consequence of bottom-up sensory processing or predicated on top-down influence is debated. We show that the neural computation of attentional pop-out is embedded in the earliest cortical sensory response, seemingly void of feedback from higher-level areas. We measured synaptic and spiking activity across cortical columns in mid-level area V4 of monkeys searching for an attention-grabbing stimulus. Indexed by reaction times and behavioral accuracy, attention was captured at variable times. This moment of attentional capture occurred within the earliest feedforward response, both in terms of timing and spatial location. Moreover, the magnitude of the earliest sensory response predicted reaction times. Crucially, errant attentional selection and consequent behavior was associated with errant selection in sensory cortex. Together, these findings demonstrate a dominant role for feedforward activation of sensory cortex for dictating attentional priority and subsequent behavior. In brief Why do certain objects stand out from their surroundings and seemingly grab our attention? In this study, Westerberg et al. determine that attentional selection for salient objects in our environment is computed in sensory cortex as soon as sensory information arrives. Highlights Early sensory responses in V4 predict attentional selection and behavioral responses Errant attentional selection in sensory cortex precedes errant behavior Tonic modulation of sensory cortex can regulate attentional selection
An atypical F-actin capping protein modulates cytoskeleton behaviors crucial to colonization of Trichomonas vaginalis

Cytoadherence and consequential migration are crucial for pathogens to establish colonization in the host. In contrast to the nonadherent isolate of Trichomonas vaginalis, the adherent one expresses more actin-related machinery proteins with more active flagellate-amoeboid morphogenesis, amoeba migration, and cytoadherence, activities that were abrogated by an actin assembly blocker. By immunoprecipitation coupled with label-free quantitative proteomics, an F-actin capping protein (TvFACPα) was identified from the actin-centric interactome, with an atypically greater binding preference to G-actin than F-actin. TvFACPα partially colocalized with F-actin at the parasite pseudopodia protrusion and formed the protein complexes with α-actin through its c-terminal domain. Meanwhile, TvFACPα overexpression suppresses F-actin polymerization, amoeboid morphogenesis, and cytoadherence in this parasite. Ser2 phosphorylation of TvFACPα enriched in the amoeboid stage of adhered trophozoites was reduced by a CKII inhibitor. The site-directed mutagenesis and CKII inhibitor treatment revealed that Ser2 phosphorylation acts as a switching signal to alter TvFACPα actin-binding activity and consequent actin cytoskeleton behaviors. Through CKII signaling, TvFACPα also controls the conversion of adherent trophozoite from amoeboid migration to flagellate form with axonemal motility. Together, CKII-dependent Ser2 phosphorylation regulates TvFACPα binding actin to fine-tune cytoskeleton dynamics and drive crucial behaviors underlying host colonization of T. vaginalis.
Docking-based long timescale simulation of cell-size protein systems at atomic resolution

Computational methodologies are increasingly addressing modeling of the whole cell at the molecular level. Proteins and their interactions are the key component of cellular processes. Techniques for modeling protein interactions, so far, have included protein docking and molecular simulation. The latter approaches account for the dynamics of the interactions, but are relatively slow, if carried out at all-atom resolution, or are significantly coarse-grained. Protein docking algorithms are far more efficient in sampling spatial coordinates. However, they do not account for the kinetics of the association (i.e., they do not involve the time coordinate). Our proof-of-concept study bridges the two modeling approaches, developing an approach that can reach unprecedented simulation timescales at all-atom resolution. The global intermolecular energy landscape of a large system of proteins was mapped by the pairwise Fast Fourier Transform docking and sampled in space and time by Monte Carlo simulations. The simulation protocol was parametrized on existing data and validated on a number of observations from experiments and molecular dynamics simulations. The simulation protocol performed consistently across very different systems of proteins at different protein concentrations. It recapitulated data on the previously observed protein diffusion rates and aggregation. The speed of calculation allows reaching second-long trajectories of protein systems that approach the size of the cells, at atomic resolution.
Mesopredator-mediated trophic cascade can break persistent phytoplankton blooms in coastal waters

Managing eutrophied systems only bottom-up (nutrient decreases) can be economically and ecologically challenging. Top-down controls (consumption) were sometimes found to effectively control phytoplankton blooms. However, mechanistic insights, especially on possible trophic cascades, are less understood in brackish, species-poor coastal waters, where large cladocera are absent. In this study, we set-up large mesocosms for three consecutive years during growth season. One set of mesocosms was controlled by mesopredator (gobies and shrimp), whereas the other mesocosms had no such mesopredator present. The results were standardized to monitoring data of the ecosystem to denote possible differences between treatments and the system. We found that mesopredator mesocosms showed lower turbidity, phytoplankton biomass, and nutrients compared to no-mesopredator mesocosms and the ecosystem. This decrease allowed macrophytes to colonize water depths only sparsely colonized in the ecosystem. Rotifer biomass increased in mesopredator mesocosms compared to the ecosystem and no-mesopredator mesocosms. Likewise, copepod biomass that potentially grazes upon rotifers and other microzooplankton decreased in mesopredator mesocosms. No-mesopredator mesocosms were colonized by an omnivorous mesograzer (Gammarus tigrinus), potentially creating additional pressure on macrophytes and increasing grazing-mediated nutrient release. Zooplankton was not able to control the non-nutrient limited phytoplankton. We propose a new mechanism, where a higher mesopredator density will increase grazing on phytoplankton by promoting microzooplankton capable of grazing on picophytoplankton. This proposed mechanism would contrast with freshwater systems, where a decrease of zooplanktivorous fish would promote larger phytoplankton grazer like cladocera. Biomanipulation in such species-poor eutrophic coastal waters may be more successful, due to less trophic pathways that can cause complex top-down controls. Stocking eutrophic coastal waters with gobies and shrimps may be an alternative biomanipulative approach rather than selectively remove large piscivorous or omnivorous fish from eutrophic coastal waters.
Defective synaptic plasticity in a model of Coffin–Lowry syndrome is rescued by simultaneously targeting PKA and MAPK pathways

Empirical and computational methods were combined to examine whether individual or dual-drug treatments can restore the deficit in long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse observed in a molecular model of Coffin-Lowry Syndrome (CLS). The model was produced by pharmacological inhibition of p90 ribosomal S6 kinase (RSK) activity. Simultaneous treatment with an activator of the mitogen-activated protein kinase (MAPK) isoform ERK and an activator of protein kinase A (PKA) resulted in enhanced phosphorylation of RSK and LTF to a greater extent than either drug alone and greater than their additive effects. Indeed, the combined drugs exerted synergistic effects on both RSK activation and LTF, fully restoring RSK phosphorylation and LTF. The extent of synergism appeared to depend on another MAPK isoform, p38 MAPK. Inhibition of p38 MAPK facilitated serotonin (5-HT)-induced RSK phosphorylation, indicating that p38 MAPK inhibits activation of RSK. Inhibition of p38 MAPK combined with activation of PKA synergistically activated RSK.
ARF6 is a host factor for SARS-CoV-2 infection in vitro

SARS-CoV-2 is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors, and the mechanism of fusion of the virus at the plasma membrane have been extensively investigated, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but dependent on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and it is involved in the entry and infection of several pathogenic viruses. Using CRISPR-Cas9 genetic deletion, we observed that ARF6 is important for SARS-CoV-2 uptake and infection in Huh-7. This finding was corroborated using a pharmacologic inhibitor, whereby the ARF6 inhibitor NAV-2729 showed a dose-dependent inhibition of viral infection. Importantly, NAV-2729 reduced SARS-CoV-2 viral loads also in more physiologic models of infection: Calu-3 and kidney organoids. This highlighted the importance of ARF6 in multiple cell contexts. Together, these experiments points to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.
Lymphoma cells are circulating in blood of Enzootic Bovine Leukosis and clonality value of virus-infected cells is a useful information for the diagnostic test

Bovine leukemia virus (BLV), a retrovirus, causes Enzootic Bovine Leukosis (EBL) in cattle following a latent infection period. The BLV infection results in polyclonal expansion of infected B-lymphocytes and ∼5% of infected cattle develop monoclonal leukosis. Since the clonal expansion of virus-infected cell is a key in the pathogenesis of EBL, assessing the clonality of malignant cells is crucial for both understanding viral pathogenesis, which might be useful for EBL diagnosis. For the investigation of clonality of BLV-infected cells in non-EBL and EBL cattle, two methods were used to evaluate the status of EBL; BLV-DNA-capture-seq method with high sensitivity and specificity and simple and cost-effective Rapid Amplification of Integration Site for BLV (BLV-RAIS) method. We found that the RAIS method efficiently detect expanded clone in EBL tissue sample as BLV-DNA-capture-seq method. Taking advantage of high frequency of BLV-infected cells in blood, we simplified RAIS method and showed that similar to BLV-DNA-capture-seq, this method could reliably provide quantitative value about clonal abundance of BLV-infected cells. Next, we aimed to establish a diagnostic blood test for EBL by using the clonality information. First, we compared clonality of BLV-infected cells in blood with that in tumor tissue in EBL cattle. There was a remarkably similar clonality between blood and tissue in each animal. Furthermore, BLV integration site information clearly showed that the same clone was the most expanded in both blood and tumor tissue, indicating that tumor cells were circulating in blood in the disease cattle. We also analyzed tumor tissue at two independent anatomical regions and found the same clones was most expanded in both regions, supporting the idea that tumor cells are systemically circulating in the diseased cattle. Finally, we compared clonality value between non-EBL and EBL cattle by using BLV-RAIS method and found that there was clear difference between non-EBL and EBL. More importantly, we found that clonality value was low in asymptomatic phase but high in EBL phase in the longitudinal cohort study. These findings have demonstrated that BLV integration site and clonality value are is a useful information to establish diagnostic blood test for EBL. That would contribute to reduction of economic damage caused by EBL and improvement of productivity in cattle industry.
Decreasing photosystem antenna size: a double-edged sword for canopy photo-synthetic efficiency

Optimization of antenna size of photosynthetic systems is one strategy to increase plant canopy photosynthesis and crop yield potential. The relationship between antenna size and photosynthesis rate has been extensively studied recently. However, conflicting results have been obtained. Here we show that the extent of decrease in antenna size is a major factor determining the consequences of decreasing antenna on photosynthesis and growth-related parameters. Specifically, we constructed transgenic rice lines with artificial microRNA (amiRNA) targeting to Chlorophyll Synthesis (YGL1) to generate transgene heterozygous and homozygous lines with different leaf chlorophyll contents and antenna sizes. We found that canopy photosynthesis (Ac), biomass and grain yield of the heterozygote were not significantly different from those of WT while the Ac, biomass and grain yield of the homozygote were lower than those of WT. Further, when the maximal quantum yield of photosystem II (Fv/Fm) was larger than 0.8, decreasing antenna size by reducing chlorophyll biosynthesis did not affect leaf photosynthesis; but when Fv/Fm was lower than 0.8, there is a positive relationship between antenna size and leaf photosynthesis. There is large variation in both leaf chlorophyll content and antenna size in elite rice cultivars, suggesting that there is a large scope to decrease leaf chlorophyll content to increase nitrogen use efficiency as long as the quantum yield of PSII is not compromised.
Emergent Actin Flows Explain Diverse Parasite Gliding Modes

During host infection, single-celled apicomplexan parasites like Plasmodium and Toxoplasma use a motility mechanism called gliding, which differs fundamentally from other known mechanisms of eukaryotic cell motility. Gliding is thought to be powered by a thin layer of flowing filamentous (F)-actin1– 3 sandwiched between the plasma membrane and a myosin-coated4,5 inner membrane complex. How this surface actin layer drives the diverse apicomplexan gliding modes observed experimentally - helical, circular, and twirling6,7, and patch8, pendulum9, or rolling2 – presents a rich biophysical puzzle. Here, we use single-molecule imaging to track individual actin filaments and myosin complexes in live Toxoplasma gondii. Based on these data, we hypothesize that F-actin flows arise by self-organization, rather than following a microtubule-based template as previously believed. We develop a continuum model of emergent F-actin flow within the unusual confines provided by parasite geometry. In the presence of F-actin turnover, our model predicts the emergence of a steady-state mode in which actin transport is largely rearward. Removing actin turnover leads to actin patches that recirculate up and down the cell, a “cyclosis” that we observe experimentally for drug-stabilized actin bundles in live parasites. These findings provide a mechanism by which actin turnover governs a transition between distinct self-organized F-actin states, whose properties can account for the diverse gliding modes known to occur. More broadly, we illustrate how different forms of gliding motility can emerge as an intrinsic consequence of the self-organizing properties of F-actin flow in a confined geometry.
Lysine 27 of histone H3.3 is a fine modulator of developmental gene expression and stands as an epigenetic checkpoint for lignin biosynthesis in Arabidopsis

Chromatin is a dynamic platform within which gene expression is controlled by epigenetic modifications, notably targeting amino acid residues of histone H3. Among them is Lysine 27 of H3 (H3K27), which trimethylation by the Polycomb Repressive Complex 2 (PRC2) is instrumental in regulating spatio-temporal patterns of key developmental genes. H3K27 is also subjected to acetylation, found at sites of active transcription. Most information on the function of histone residues and their associated modifications in plants was obtained from studies of loss-of-function mutants for the complexes that modify them. In order to decrypt the genuine function of H3K27, we expressed a non-modifiable variant of H3 at residue K27 (H3.3K27A) in Arabidopsis, and developed a multi-scale approach combining in-depth phenotypical and cytological analyses, with transcriptomics and metabolomics. We uncovered that the H3.3K27A variant causes severe developmental defects, part of them reminiscent of PRC2 mutants, part of them new. They include early flowering, increased callus formation, and short stems with thicker xylem cell layer. This latest phenotype correlates with mis-regulation of phenylpropanoid biosynthesis. Overall, our results reveal novel roles of H3K27 in plant cell fates and metabolic pathways, and highlight an epigenetic control point for elongation and lignin composition of the stem.
Synthetic lethality-based prediction of cancer treatment response from histopathology images

Advances in artificial intelligence have paved the way for predicting cancer patients’ survival and response to treatment from hematoxylin and eosin (H&E)-stained tumor slides. Extant approaches do so either directly from the H&E images or via prediction of actionable mutations and gene fusions. Here we present the first genetic interactions (GI)-based approach for predicting patient response to treatment, founded on two conceptual steps: (1) First, we build DeepPT, a deep-learning framework that predicts tumor gene expression from H&E slides, and subsequently, (2) we apply ENLIGHT - a previously published GI based approach - to predict patient treatment response from the inferred tumor expression. DeepPT was trained on images and corresponding transcriptomics data of TCGA breast, kidney, lung, and brain tumor samples. Testing DeepPT transcriptomics prediction ability, we find that it generalizes well to predicting the expression of two breast and brain cancer unseen independent datasets. Studying samples from a recently published large multi-omics breast cancer clinical trial, we applied ENLIGHT to the expression predicted by DeepPT from the tumor slides. We find that it successfully predicts true responders
Quantitative trait locus mapping of osmotic stress response in the fungal wheat pathogen Zymoseptoria tritici

Osmotic stress is a ubiquitous and potent stress for all living organisms, but few studies have investigated the genetic basis of salt tolerance in filamentous fungi. The main aim of this study was to identify regions of the genome associated with tolerance to potassium chloride in the wheat pathogen Zymoseptoria tritici. A secondary aim was to identify candidate genes affecting salt tolerance within the most promising chromosomal regions. We achieved these aims with a quantitative trait locus (QTL) mapping study using offspring from two crosses grown in vitro in the presence or absence of osmotic stress imposed by 0.75M KCl. We identified significant QTL for most of the traits in both crosses. Several QTL overlapped with QTL identified in earlier studies for other traits and some QTL explained trait variation in both the control and salt stress environments. A significant QTL on chromosome 3 explained variation in colony radius at 8 days post inoculation (dpi) in the KCl environment as well as colony radius KCl tolerance at 8 dpi. The QTL peak had a high LOD and encompassed an interval containing only 36 genes. Six of these genes present promising candidates for functional analyses. A GO enrichment analysis of QTL unique to the KCl environment found evidence for enrichment of functions involved in osmotic stress responses.
Oxygenation In Curing A Young Man Post-Operative of The Modi ed Fontan Operation

Hebing Guo Capital Medical University Jianbo Tan Capital Medical University Yongchao Cui Capital Medical University Haofeng Xiong Capital Medical University Chuansheng Li Capital Medical University Yufeng Liu Capital Medical University Yao Sun Capital Medical University Lin Pu Capital Medical University Pan Xiang Capital Medical University Ming Zhang Capital Medical University Jingjing Hao Capital Medical University Ningning Yin Capital Medical University Xiaotong Hou Capital Medical University Jingyuan Liu (  dtyyicu@ccmu.edu.cn ) Capital Medical University https://orcid.org/0000-0002-0592-9789