Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation and Molecular Basis for Enhancement of Receptor Binding of H9N2 Avian Influenza Viruses in China Isolates

Currently, H9N2 avian influenza viruses (H9N2 AIVs) globally circulate in poultry and have acquired some adaptation to mammals. However, it is not clear what the molecular basis is for the variation in receptor-binding features of the H9N2 AIVs. The receptor-binding features of 92 H9N2 AIVs prevalent in China during 1994–2017 were characterized through solid-phase ELISA assay and reverse genetics. H9N2 AIVs that circulated in this period mostly belonged to clade h9.4. 2. Two increasing incidents occurred in the ability of H9N2 AIVs to bind to avian-like receptors in 2002–2005 and 2011–2014. Two increasing incidents occurred in the strength of H9N2 AIVs to bind to human-like receptors in 2002–2005 and 2011–2017. We found that Q227M, D145G/N, S119R, and R246K mutations can significantly increase H9N2 AIVs to bind to both avian- and human-like receptors. A160D/N, Q156R, T205A, Q226L, V245I, V216L, D208E, T212I, R172Q, and S175N mutations can significantly enhance the strength of H9N2 AIVs to bind to human-like receptors. Our study also identified mutations T205A, D208E, V216L, Q226L, and V245I as the key sites leading to enhanced receptor binding of H9N2 AIVs during 2002–2005 and mutations S119R, D145G, Q156R, A160D, T212I, Q227M, and R246K as the key sites leading to enhanced receptor binding of H9N2 AIVs during 2011–2017. These findings further illustrate the receptor-binding characteristics of avian influenza viruses, which can be a potential threat to public health.
Drug Repositioning Screen on a New Primary Cell Line Identifies Potent Therapeutics for Glioblastoma

Glioblastoma is a malignant brain cancer with limited treatment options and high mortality rate. While established glioblastoma cell line models provide valuable information, they ultimately lose most primary characteristics of tumors under long-term serum culture conditions. Therefore, established cell lines do not necessarily recapitulate genetic and morphological characteristics of real tumors. In this study, in line with the growing interest in using primary cell line models derived from patient tissue, we generated a primary glioblastoma cell line, KUGBM8 and characterized its genetic alterations, long term growth ability, tumor formation capacity and its response to Temozolomide, the front-line chemotherapy utilized clinically. In addition, we performed a drug repurposing screen on the KUGBM8 cell line to identify FDA-approved agents that can be incorporated into glioblastoma treatment regimen and identified Topotecan as a lead drug among 1,200 drugs. We showed Topotecan can induce cell death in KUGBM8 and other primary cell lines and cooperate with Temozolomide in low dosage combinations. Together, our study provides a new primary cell line model that can be suitable for both in vitro and in vivo studies and suggests that Topotecan can offer promise as a therapeutic approach for glioblastoma.
Excessive and Problematic Internet Use During the Coronavirus Disease 2019 School Closure: Comparison Between Japanese Youth With and Without Autism Spectrum Disorder

Internet use in the youth has increased manifold during the coronavirus disease 2019 (COVID-19) pandemic. Individuals with autism spectrum disorder (ASD) generally have a higher risk of problematic internet use. The aim of this study is to investigate the differences in internet and related digital media use between children with ASD and their typically developing counterparts during the COVID-19 pandemic. In this online survey in Japan conducted from April 30 to May 8, 2020, we analyzed digital media time of 84 children with ASD and 361 age- and gender-matched controls before and after school closure. Digital media use duration was significantly longer in the ASD group than in the control group before the pandemic. The increase of media use time was more prominent in the control group than in the ASD group. We observed excessive Internet use among children with ASD and without ASD, especially during the COVID-19 pandemic. It is necessary to establish strategies to prevent excessive internet use in not only children and adolescents with ASD but also without ASD in the post-pandemic world.
Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-Associated Protein 9 Mediated Knockout Reveals Functions of the yellow-y Gene in Spodoptera litura

Yellow genes are thought to be involved in the melanin biosynthetic pathway and play a crucial role in pigmentation reactions in insects. However, little research has been done on yellow genes in lepidopteran pests. To clarify the function of one of the yellow genes (yellow-y) in Spodoptera litura, we cloned the full-length of yellow-y, and investigated its spatial and temporal expression profiles by quantitative real-time PCR (qPCR). It revealed that yellow-y was highly expressed in larva of fourth, fifth, and sixth instars, as well as in epidermis (Ep), fat bodies (FB), Malpighian tubes (MT), and midguts (MG) of the larvae; whereas it was expressed in very low levels in different tissues of adults, and was almost undetected in pupa. This expression profile suggests an important role of yellow-y in larvae, minor role in adults, and no role in pupae. To confirm this, we disrupted yellow-y using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, and obtained G0 insects with mutation in yellow-y. The mutation in yellow-y clearly rendered the larvae body, a color yellower than that of wide type insects, and in addition, the mutation resulted in abnormal segmentation and molting for older larvae. The mutation of yellow-y also made various adult tissues (antennae, proboscis, legs, and wings) yellowish. However, the mutation had no effect on pigmentation of the pupal cuticle. Taken together, our study clearly demonstrated the role of yellow-y not only in the body pigmentation of larvae and adults, and but also in segmentation and molting of larvae, providing new insights into the physiology of larval development, as well as a useful marker gene for genome editing based studies.
Caspase-8 Inhibition Prevents the Cleavage and Degradation of E3 Ligase Substrate Receptor Cereblon and Potentiates Its Biological Function

Cereblon (CRBN), a substrate receptor of cullin 4-RING E3 ligase (CRL4), mediates the ubiquitination and degradation of constitutive substrates and immunomodulatory drug-induced neo-substrates including MEIS2, c-Jun, CLC1, IKZF1/3, CK1α, and SALL4. It has been reported that CRBN itself could be degraded through the ubiquitin-proteasome system by its associated or other cullin-RING E3 ligases, thus influencing its biological functions. However, it is unknown whether the CRBN stability and its biological function could be modulated by caspases. In this study, using model cell lines, we found that activation of the death receptor using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) leads to the decreased CRBN protein level. Through pharmacological inhibition and activation of caspase-8 (CASP-8), we disclosed that CASP-8 regulates CRBN cleavage in cell lines. Site mapping experiments revealed that CRBN is cleaved after Asp9 upon CASP-8 activation, resulting in the reduced stability. Using myeloma as a model system, we further revealed that either inhibition or genetic depletion of CASP-8 enhances the anti-myeloma activity of lenalidomide (Len) by impairing CRBN cleavage, leading to the attenuated IKZF1 and IKZF3 protein levels and the reduced viability of myeloma cell lines and primary myeloma cells from patients. The present study discovered that the stability of the substrate receptor of an E3 ligase can be modulated by CASP-8 and suggested that administration of CASP-8 inhibitors enhances the overall effectiveness of Len-based combination therapy in myeloma.
Perinatal Derivatives: Where Do We Stand? A Roadmap of the Human Placenta and Consensus for Tissue and Cell Nomenclature

Progress in the understanding of the biology of perinatal tissues has contributed to the breakthrough revelation of the therapeutic effects of perinatal derivatives (PnD), namely birth-associated tissues, cells, and secreted factors. The significant knowledge acquired in the past two decades, along with the increasing interest in perinatal derivatives, fuels an urgent need for the precise identification of PnD and the establishment of updated consensus criteria policies for their characterization. The aim of this review is not to go into detail on preclinical or clinical trials, but rather we address specific issues that are relevant for the definition/characterization of perinatal cells, starting from an understanding of the development of the human placenta, its structure, and the different cell populations that can be isolated from the different perinatal tissues. We describe where the cells are located within the placenta and their cell morphology and phenotype. We also propose nomenclature for the cell populations and derivatives discussed herein. This review is a joint effort from the COST SPRINT Action (CA17116), which broadly aims at approaching consensus for different aspects of PnD research, such as providing inputs for future standards for the processing and in vitro characterization and clinical application of PnD.
Hyperscanning EEG and Classification Based on Riemannian Geometry for Festive and Violent Mental State Discrimination

Interactions between two brains constitute the essence of social communication. Daily movements are commonly executed during social interactions and are determined by different mental states that may express different positive or negative behavioral intent. In this context, the effective recognition of festive or violent intent before the action execution remains crucial for survival. Here, we hypothesize that the EEG signals contain the distinctive features characterizing movement intent already expressed before movement execution and that such distinctive information can be identified by state-of-the-art classification algorithms based on Riemannian geometry. We demonstrated for the first time that a classifier based on covariance matrices and Riemannian geometry can effectively discriminate between neutral, festive, and violent mental states only on the basis of non-invasive EEG signals in both the actor and observer participants. These results pave the way for new electrophysiological discrimination of mental states based on non-invasive EEG recordings and cutting-edge machine learning techniques.
Emotional Labor in Health Care: The Moderating Roles of Personality and the Mediating Role of Sleep on Job Performance and Satisfaction

The objective of this study is to investigate the effects of emotional labor on job performance and satisfaction, as well as to examine the mediating effect of sleep problems and the moderating effects of personality traits. A time-lagged study was conducted on 864 health professionals. Scales for emotional labor, sleep, personality traits, and job satisfaction were used and job performance data was obtained from records maintained by human resources. Structural equation modeling was performed to investigate the relations. Sleep problems only partially mediated the relationship between surface acting and job satisfaction but completely mediated the relationship between surface acting and job performance. Several personality traits were shown to moderate the relationship between surface acting and sleep problems. The effects were stronger for people with low agreeableness and high neuroticism. The relationship between high levels of deep acting and low levels of sleep problems was more pronounced in individuals with low extraversion. Supervisors should be conscious of emotional labor in the work context and provide necessary deep acting training to facilitate emotional regulation.
Sex Differences in the Pro-Angiogenic Response of Human Endothelial Cells: Focus on PFKFB3 and FAK Activation

Female hormones and sex-specific factors are established determinants of endothelial function, yet their relative contribution to human endothelium phenotypes has not been defined. Using human umbilical vein endothelial cells (HUVECs) genotyped by donor's sex, we investigated the influence of sex and estrogenic agents on the main steps of the angiogenic process and on key proteins governing HUVEC metabolism and migratory properties. HUVECs from female donors (fHUVECs) showed increased viability (p < 0.01) and growth rate (p < 0.01) compared with those from males (mHUVECs). Despite higher levels of G-protein coupled estrogen receptor (GPER) in fHUVECs (p < 0.001), treatment with 17β-estradiol (E2) and the selective GPER agonist G1 (both 1–100 nM) did not affect HUVEC viability. Migration and tubularization in vitro under physiological conditions were higher in fHUVECs than in mHUVECs (p < 0.05). E2 treatment (1–100 nM) upregulated the glycolytic activator PFKFB3 with higher potency in fHUVECs than in mHUVECs, despite comparable baseline levels. Moreover, Y576/577 phosphorylation of focal adhesion kinase (FAK) was markedly enhanced in fHUVECs (p < 0.001), despite comparable Src activation levels. While the PI3K inhibitor LY294002 (25 µM) inhibited HUVEC migration (p < 0.05), Akt phosphorylation levels in fHUVECs and mHUVECs were comparable. Finally, digitoxin treatment, which inhibits Y576/577 FAK phosphorylation, abolished sexual dimorphism in HUVEC migration. These findings unravel complementary modulation of HUVEC functional phenotypes and signaling molecules involved in angiogenesis by hormone microenvironment and sex-specific factors, and highlight the need for sex-oriented pharmacological targeting of endothelial function.
Direct Methanation of Biogas—Technical Challenges and Recent Progress

The direct methanation of biogas using hydrogen from electrolysis is a promising pathway for seasonal storage of renewables in the natural gas network. It offers particular advantages over the methanation of carbon dioxide separated from biogas, as it eliminates a costly and unnecessary carbon dioxide separation step. The key implementation challenges facing direct methanation of biogas are reviewed here: 1) treatment of biogas impurities; 2) competing reactor concepts for methanation; and 3) competing process concepts for final upgrading. For each of these three aspects, the state of the art is reviewed, focusing especially on results which have been validated at a high Technology Readiness Level (TRL) at recent long-duration demonstrations. The different technology solutions have advantages and disadvantages which may fit best to different technical and economic boundary conditions, which are discussed. As a final outlook, TRL 8 demo plants will be necessary to show the full potential of these systems, and to obtain consistent operation data to allow a cost comparison.
Genetic Mapping of Climbing and Mimicry: Two Behavioral Traits Degraded During Silkworm Domestication

Behavioral changes caused by domestication in animals are an important issue in evolutionary biology. The silkworm, Bombyx mori, is an ideal fully domesticated insect model for studying both convergent domestication and behavior evolution. We explored the genetic basis of climbing for foraging and mimicry, two degraded behaviors during silkworm domestication, in combination of bulked segregant analysis (BSA) and selection sweep screening. One candidate gene, ASNA1, located in the 3–5 Mb on chromosome 19, harboring a specific non-synonymous mutation in domestic silkworm, might be involved in climbing ability. This mutation was under positive selection in Lepidoptera, strongly suggesting its potential function in silkworm domestication. Nine candidate domesticated genes related to mimicry were identified on chromosomes 13, 21, and 27. Most of the candidate domesticated genes were generally expressed at higher levels in the brain of the wild silkworm. This study provides valuable information for deciphering the molecular basis of behavioral changes associated with silkworm domestication.
Identification and enhancement of antioxidant P1-peptide isolated from Ganoderma lucidum hydrolysate

ABSTRACT Ganoderma lucidum is an edible fungus which typically used in functional food products because of the potential enhancement of health. Many hydrolysates from G. lucidum exhibit various biological functions. Using LC-MS/MS, the peptide sequence was predicted based on the de novo sequencing algorithm and P1-peptide (VDLPTCKGF) was identified. The peptide was modified by shortening C-terminal residue one at a time until three residues remained, and chemically synthesized all modified peptides by SPPS. Seven-synthetic peptides were purified and molecularly evaluated by HPLC and LC-MS. The antioxidant capacity of these peptides was evaluated, while also the intracellular-ROS was detected to validate the antioxidant activity. This study showed that 3 of 7 synthetic peptides had in vitro antioxidant activity and suppressed intracellular-ROS. Among all modified peptides, VDLPTC exhibited the highest antioxidant capacity and revealed intracellular-ROS suppression. This evidence reflects their radical-scavenging activities and provides the rationale for the development of novel functional food ingredients.
Effect of Temperature on Acetate Mineralization Kinetics and Microbial Community Composition in a Hydrocarbon-Affected Microbial Community During a Shift From Oxic to Sulfidogenic Conditions

Aquifer thermal energy storage (ATES) allows for the seasonal storage and extraction of heat in the subsurface thus reducing reliance on fossil fuels and supporting decarbonization of the heating and cooling sector. However, the impacts of higher temperatures toward biodiversity and ecosystem services in the subsurface environment remain unclear. Here, we conducted a laboratory microcosm study comprising a hydrocarbon-degrading microbial community from a sulfidic hydrocarbon-contaminated aquifer spiked with 13C-labeled acetate and incubated at temperatures between 12 and 80°C to evaluate (i) the extent and rates of acetate mineralization and (ii) the resultant temperature-induced shifts in the microbial community structure. We observed biphasic mineralization curves at 12, 25, 38, and 45°C, arising from immediate and fast aerobic mineralization due to an initial oxygen exposure, followed by slower mineralization at sulfidogenic conditions. At 60°C and several replicates at 45°C, acetate was only aerobically mineralized. At 80°C, no mineralization was observed within 178 days. Rates of acetate mineralization coupled to sulfate reduction at 25 and 38°C were six times faster than at 12°C. Distinct microbial communities developed in oxic and strictly anoxic phases of mineralization as well as at different temperatures. Members of the Alphaproteobacteria were dominant in the oxic mineralization phase at 12–38°C, succeeded by a more diverse community in the anoxic phase composed of Deltaproteobacteria, Clostridia, Spirochaetia, Gammaproteobacteria and Anaerolinea, with varying abundances dependent on the temperature. In the oxic phases at 45 and 60°C, phylotypes affiliated to spore-forming Bacilli developed. In conclusion, temperatures up to 38°C allowed aerobic and anaerobic acetate mineralization albeit at varying rates, while mineralization occurred mainly aerobically between 45 and 60°C; thermophilic sulfate reducers being active at temperatures > 45°C were not detected. Hence, temperature may affect dissolved organic carbon mineralization rates in ATES while the variability in the microbial community composition during the transition from micro-oxic to sulfidogenic conditions highlights the crucial role of electron acceptor availability when combining ATES with bioremediation.
Harvesting electricity from benzene and ammonium-contaminated groundwater using a microbial fuel cell with an aerated cathode

Groundwater contaminated with benzene and ammonium was continuously treated using a microbial fuel cell (MFC) with an aerated cathode and a control without aeration at the cathode. Benzene (∼15 mg L−1) was completely removed in the MFC of which 80% disappeared at the anoxic anode. Ammonium (∼20 mg L−1) was oxidized to nitrate at the cathode, which was not directly linked to electricity generation. The maximum power density was 316 mW m−3 NAC at a current density of 0.99 A m−3 normalized by the net anodic compartment (NAC). Coulombic and energy efficiencies of 14% and 4% were obtained based on the anodic benzene degradation. The control reactor failed to generate electricity, and can be regarded as a mesocosm in which granular graphite was colonized by benzene degraders with a lower benzene removal efficiency compared to the MFC. The dominance of phylotypes affiliated to Chlorobiaceae, Rhodocyclaceae and Comamonadaceae was revealed by 16S rRNA illumina sequencing in the control and the MFC anode, presumably associated with benzene degradation. Ammonium oxidation at the cathode of the MFC was mainly carried out by phylotypes belonging to the Nitrosomonadales and Nitrospirales. Compound specific isotope analysis (CSIA) indicated that benzene degradation was initially activated by monohydroxylation with molecular oxygen. The intermediates of the benzene degradation pathway were subsequently oxidized accompanied by transferring electrons to the anode, leading to current production. This study provided valuable insights into the application of MFCs to treat groundwater contaminated with petroleum hydrocarbons (e.g. benzene) and ammonium.
Cooperative changes in solvent exposure identify cryptic pockets, conformational switches, and allosteric coupling

Proteins are dynamic molecules that undergo conformational changes to a broad spectrum of different excited states. Unfortunately, the small populations of these states make it difficult to determine their structures or functional implications. Computer simulations are an increasingly powerful means to identify and characterize functionally-relevant excited states. However, this advance has uncovered a further challenge: it can be extremely difficult to identify the most salient features of large simulation datasets. We reasoned that many functionally-relevant conformational changes are likely to involve large, cooperative changes to the surfaces that are available to interact with potential binding partners. To examine this hypothesis, we introduce a method that returns a prioritized list of potentially functional conformational changes by segmenting protein structures into clusters of residues that undergo cooperative changes in their solvent exposure, along with the hierarchy of interactions between these groups. We term these groups exposons to distinguish them from other types of clusters that arise in this analysis and others. We demonstrate, using three different model systems, that this method identifies experimentally-validated and functionally-relevant conformational changes, including conformational switches, allosteric coupling, and cryptic pockets. Our results suggest that key functional sites are hubs in the network of exposons. As a further test of the predictive power of this approach, we apply it to discover cryptic allosteric sites in two different β-lactamase enzymes that are widespread sources of antibiotic resistance. Experimental tests confirm our predictions for both systems. Importantly, we provide the first evidence for a cryptic allosteric site in CTX-M-9 β-lactamase. Experimentally testing this prediction did not require any mutations, and revealed that this site exerts the most potent allosteric control over activity of any pockets found in β-lactamases to date. Discovery of a similar pocket that was previously overlooked in the well-studied TEM-1 β-lactamase demonstrates the utility of exposons.