Miracle-dz/UniFAR-FTUs huggingface dataset:
Bud23 promotes the progression of the Small Subunit Processome to the pre-40S ribosome in Saccharomyces cerevisiae

The first metastable assembly intermediate of the eukaryotic ribosomal small subunit (SSU) is the SSU Processome, a large complex of RNA and protein factors that is thought to represent an early checkpoint in the assembly pathway. Transition of the SSU Processome towards continued maturation requires the removal of the U3 snoRNA and biogenesis factors as well as ribosomal RNA processing. While the factors that drive these events are largely known, how they do so is not well understood. The methyltransferase Bud23 has a role during this transition, but its function, beyond the nonessential methylation of 18S rRNA, is not characterized. Here, we have carried out a comprehensive genetic screen to understand Bud23 function. We identified 67 unique extragenic bud23Δ-suppressing mutations that mapped to genes encoding the SSU Processome factors DHR1, IMP4, UTP2 (NOP14), BMS1 and the SSU protein RPS28A. These factors form a physical interaction network that links the binding site of Bud23 to the U3 snoRNA and many of the suppressing mutations weaken protein-protein and protein-RNA interactions. Importantly, this network links Bud23 to the GTPase Bms1 and the RNA helicase Dhr1. Bms1 is thought to drive conformational changes to promote rRNA cleavage, and we previously showed that Dhr1 is required for unwinding the U3 snoRNA. Moreover, particles isolated from cells lacking Bud23 accumulated late SSU Processome factors and pre-rRNAs not cleaved at sites A1 and A2. We propose a model in which Bud23 dissociates factors surrounding its binding site to promote SSU Processome progression. Author summary Ribosomes are the molecular machines that synthesize proteins and are composed of a large and a small subunit which carry out the essential functions of polypeptide synthesis and mRNA decoding, respectively. Ribosome production is tightly linked to cellular growth as cells must produce enough ribosomes to meet their protein needs. However, ribosome assembly is a metabolically expensive pathway that must be balanced with other cellular energy needs and regulated accordingly. In eukaryotes, the small subunit (SSU) Processome is a metastable intermediate that ultimately progresses towards a mature SSU through the release of biogenesis factors. The decision to progress the SSU Processome is thought to be an early checkpoint in the SSU assembly pathway, but what drives this checkpoint is unknown. Previous studies suggest that Bud23 plays an uncharacterized role during SSU Processome progression. Here, we used a genetic approach to understand its function and found that Bud23 is connected to a network of factors that stabilize the particle. Interestingly, two of these factors are enzymes that facilitate structural rearrangements needed for progression. We conclude that Bud23 promotes the release of factors surrounding its binding site to drive rearrangements during the progression of the SSU Processome.
Position Estimation of a PMSM in an Electric Propulsion Ship System Based on High-Frequency Injection

To improve the operating performance of electric propulsion ships, the permanent magnet synchronous motor is commonly used as the propulsion motor. Additionally, position estimation without sensors can further improve the application range of the propulsion motor and the estimated results can represent the redundancy of measured values from mechanical sensors. In this paper, the high-frequency (HF) injection algorithm combined with the second-order generalized integrator (SOGI) is presented on the basis of analyzing the structure of the electric propulsion ship and the vector control of the motors. The position and rotor speed were estimated accurately by the approximate calculation of q-axis currents directly related to the rotor position. Moreover, the harmonics in the estimated position were effectively reduced by the introduction of the second-order generalized integrator. Then, the rotor position estimation algorithm was verified in MATLAB/Simulink by choosing different low speeds including speed reversal, increasing speed, and increasing load torque. Finally, the correctness of the proposed improved high-frequency injection algorithm based on the second-order generalized integrator was verified by the experimental propulsion permanent magnet synchronous motor (PMSM) system at low speed.
The Sole Mycobacterium smegmatis MazF Toxin Targets tRNALys to Impart Highly Selective, Codon-Dependent Proteome Reprogramming

Survival of mycobacteria, both free-living and host-dependent pathogenic species, is dependent on their ability to evade being killed by the stresses they routinely encounter. Toxin-antitoxin (TA) systems are unique to bacteria and archaea and are thought to function as stress survival proteins. Here, we study the activity of the endoribonuclease toxin derived from the MazEF TA system in Mycobacterium smegmatis, designated MazEF-ms. We first enlisted a specialized RNA-seq method, 5’ RNA-seq, to identify the primary RNA target(s) of the MazF-ms toxin. Just two tRNA species, tRNALys-UUU and tRNALys-CUU, were targeted for cleavage by MazF-ms at a single site within their anticodon sequence (UU↓U and CU↓U) to render these tRNAs nonfunctional for protein synthesis. The 5’ RNA-seq dataset also revealed hallmarks of ribosome stalling predominantly at Lys AAA codons even though both Lys tRNAs were cleaved by MazF-ms. Stalled ribosomes were then cleaved on their 5’ side by one or more RNases, resulting in very selective degradation of only those mRNAs harboring ribosomes stalled at Lys codons. This highly surgical, codon-dependent degradation of mRNA transcripts was validated using quantitative mass spectrometry of proteins that were newly synthesized during MazF-ms expression. The M. smegmatis proteome was altered as predicted, Lys AAA codon-rich proteins was downregulated while Lys AAA codon deficient proteins were upregulated. Analysis of specific subsets of proteins that were upregulated or downregulated was consistent with the growth-arrested phenotype of MazF-ms expressing cells. Curiously, the tRNA target and mechanism of action of MazF-ms paralleled that of one atypical MazF toxin in M. tuberculosis, suggesting manipulation of the levels of lysine tRNAs as the preferred conduit for reprogramming the proteomes via ribosome stalling at rare AAA codons in these GC-rich mycobacteria.
Modulating Brain Networks With Transcranial Magnetic Stimulation Over the Primary Motor Cortex: A Concurrent TMS/fMRI Study

Stimulating the primary motor cortex (M1) using transcranial magnetic stimulation (TMS) causes unique multisensory experience such as the targeted muscle activity, afferent/reafferent sensory feedback, tactile sensation over the scalp and ‘click’ sound. Although the human M1 has been intensively investigated using TMS, the experience of the M1 stimulation has not been elucidated at the whole brain. Here, using concurrent TMS/fMRI, we investigated the acute effect of the M1 stimulation of functional brain networks during task and at rest. A short 1Hz train of TMS pulses applied to individuals’ hand area in the M1 during motor execution or at rest. Employing the independent component analysis (ICA), we showed the M1 stimulation decreased the motor networks activity when the networks were engaged in the task and increased the deactivation of networks when the networks were not involved in the ongoing task. The M1 stimulation induced the activation in the key networks involved in bodily self-consciousness (BSC) including the insular and rolandic operculum systems regardless of states. The degree of activation in these networks was highest at rest compared to during task, showing the state-dependent TMS effect. Furthermore, we demonstrated that the M1 stimulation modulated other domain general networks such as the default mode network and attention network and the inter-network connectivity between these networks. Our results showed that the M1 stimulation induced the widespread changes in the brain at the targeted system as well as non-motor, remote brain networks, specifically related to the BSC. Our findings shed light on understanding the neural mechanism of the complex and multisensory experience of the M1 stimulation.
Genomic Identification of RNA Editing Through Integrating Omics Datasets and the Clinical Relevance in Hepatocellular Carcinoma

RNA editing is a widespread post-transcriptional mechanism to introduce single nucleotide changes to RNA in human cancers. Here, we characterized the global RNA editing profiles of 373 hepatocellular carcinoma (HCC) and 50 adjacent normal liver samples from The Cancer Genome Atlas (TCGA) and revealed that most editing events tend to occur in minor percentage of samples with moderate editing degrees (20–30%). Moreover, these RNA editing prefer to be A-to-I RNA editing in protein coding genes, especially in 3′UTR regions. Considering the association between DNA mutation and RNA editing, our analysis found that RNA editing maybe a complementary event for DNA mutation of HCC risk genes in HCC patients. We next identified 454 HCC-related editing sites, and many locate on the same genes with the same editing patterns. The functional consequences of editing revealed 2,086 functional editing sites and demonstrated that most editing in coding regions are non-synonymous variations. Furthermore, our results showed that editing in the 3′UTR regions tend to influence miRNA–target binding, and the editing degree seems to be negatively correlated with gene expression. Finally, we found that 46 HCC-related editing sites with consequence are able to distinguish the prognosis differences of HCC patients, suggesting their clinical relevance. Together, our results highlight RNA editing as a valuable molecular resource for investigating HCC mechanisms and clinical treatments.
Amphiphilic Cationic Macromolecules Highly Effective Against Multi-Drug Resistant Gram-Positive Bacteria and Fungi With No Detectable Resistance

The ever increasing threats of Gram-positive superbugs such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), and vancomycin-resistant Enterococccus faecium (VRE) are serious matter of concern worldwide toward public health. Such pathogens cause repeated recurrence of infections through the formation of biofilms which consist of metabolically inactive or slow growing dormant bacterial population in vast majority. Concurrently, dispersal of biofilms originates even more virulent dispersed cells responsible for pathogenesis. Along with this, fungal infections most commonly associated with Candida albicans also created a major complicacy in human healthcare. Moreover, concomitant survival of C. albicans and MRSA in a multispecies biofilms created extremely complicated polymicrobial infections. Surprisingly, infections associated with single species biofilm as well as multiple species biofilm (co-existence of MRSA and C. albicans) are almost untreatable with conventional antibiotics. Therefore, the situation demands an urgent development of antimicrobial agent which would tackle persistent infections associated with bacteria, fungi and their biofilms. Toward this goal, herein we developed a new class of branched polyethyleneimine based amphiphilic cationic macromolecules (ACMs) bearing normal alkyl, alkyl ester and alkyl amide moieties. An optimized compound with dual activity against drug-resistant bacteria (MIC = 2–4 μg/mL) and fungi (MIC = 4–8 μg/mL) was identified with minimal toxicity toward human erythrocytes (HC50 = 270 μg/mL). The lead compound, ACM-AHex (12) displayed rapid bactericidal and fungicidal kinetics (>5 log CFU/mL reduction within 1–4 h). It also killed metabolically dormant stationary (MRSA and VRE) and persister (S. aureus) cells. Moreover, this compound was able to disrupt the preformed biofilm of MRSA and reduced the bacterial burden related to the dispersed cells. It showed significant proficiencies to eliminate polymicrobial biofilms of MRSA and C. albicans. Bacteria also could not develop any resistant against this class of membrane active molecules even after 15 days of successive passages. Taken together this class of macromolecule can be developed further as a dual therapeutic agent to combat infections associated with bacterial and fungal co-existence. Graphical Abstract Advanced weapon to tackle Polymicrobial biofilm.
Left Atrial Enlargement and the Risk of Stroke: A Meta-Analysis of Prospective Cohort Studies

Background: The association between left atrial size and the risk of stroke has not been fully understood. We performed a meta-analysis of prospective cohort studies to determine whether left atrial enlargement (LAE) is associated with an increased risk of stroke. Methods: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library through May 2019. Prospective cohort studies were included if they reported hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of stroke with respect to LAE. All meta-analyses were performed using a random-effects model. Results: Six studies involving 66,007 participants and 3,549 stroke events were included. Compared with patients without LAE, those with LAE had an increased risk of stroke (adjusted HR 1.68, 95% CI 1.36–2.07). There was also a graded association with stroke relating to LAE (adjusted HR for mild LAE 1.50, 95% CI 0.98–2.28; moderate LAE 1.40, 95% CI 1.12–1.75; and severe LAE 1.59, 95% CI 1.33–1.90). Furthermore, for each increase of 1 cm in left atrial diameter, the odds of stroke were increased by 24% (adjusted HR 1.24, 95% CI 1.03–1.50). Conclusions: Our meta-analysis demonstrated that LAE is associated with an increased and graded risk of stroke.
Enterococcus faecalis Adapts to Antimicrobial Conjugated Oligoelectrolytes by Lipid Rearrangement and Differential Expression of Membrane Stress Response Genes

Conjugated oligoelectrolytes (COEs) are emerging antimicrobials with broad spectrum activity against Gram positive and Gram negative bacteria as well as fungi. Our previous in vitro evolution studies using Enterococcus faecalis grown in the presence of two related COEs (COE1-3C and COE1-3Py) led to the emergence of mutants (changes in liaF and liaR) with a moderate 4- to16-fold increased resistance to COEs. The contribution of liaF and liaR mutations to COE resistance was confirmed by complementation of the mutants, which restored sensitivity to COEs. To better understand the cellular target of COEs, and the mechanism of resistance to COEs, transcriptional changes associated with resistance in the evolved mutants were investigated in this study. The differentially transcribed genes encoded membrane transporters, in addition to proteins associated with cell envelope synthesis and stress responses. Genes encoding membrane transport proteins from the ATP binding cassette superfamily were the most significantly induced or repressed in COE tolerant mutants compared to the wild type when exposed to COEs. Additionally, differences in the membrane localization of a lipophilic dye in E. faecalis exposed to COEs suggested that resistance was associated with lipid rearrangement in the cell membrane. The membrane adaptation to COEs in EFC3C and EFC3Py resulted in an improved tolerance to bile salt and sodium chloride stress. Overall, this study showed that bacterial cell membranes are the primary target of COEs and that E. faecalis adapts to membrane interacting COE molecules by both lipid rearrangement and changes in membrane transporter activity. The level of resistance to COEs suggests that E. faecalis does not have a specific response pathway to elicit resistance against these molecules and this is supported by the rather broad and diverse suite of genes that are induced upon COE exposure as well as cross-resistance to membrane perturbing stressors.
Linkage Analysis and Multi-Locus Genome-Wide Association Studies Identify QTNs Controlling Soybean Plant Height

Plant height is an important target for soybean breeding. It is a typical quantitative trait controlled by multiple genes and is susceptible to environmental influences. Here, we carried out phenotypic analysis of 156 recombinant inbred lines derived from “Dongnong L13” and “Henong 60” in nine environments at four locations over 6 years using interval mapping and inclusive composite interval mapping methods. We performed quantitative trait locus (QTL) analysis by applying pre-built simple-sequence repeat maps. We detected 48 QTLs, including nine significant QTLs detected by multiple methods and in multiple environments. Meanwhile, genotyping of all lines using the SoySNP660k BeadChip produced 54,836 non-redundant single-nucleotide polymorphism (SNP) genotypes. We used five multi-locus genome-wide association analysis methods to locate 10 quantitative trait nucleotides (QTNs), four of which overlap with previously located QTLs. Five candidate genes related to plant height are predicted to lie within 200 kb of these four QTNs. We identified 19 homologous genes in Arabidopsis, two of which may be associated with plant height. These findings further our understanding of the multi-gene regulatory network and genetic determinants of soybean plant height, which will be important for breeding high-yielding soybean.
Modulation of Calcium Transients in Cardiomyocytes by Transient Receptor Potential Canonical 6 Channels

Transient receptor potential canonical 6 (TRPC6) channels are non-selective cation channels that are thought to underlie mechano-modulation of calcium signaling in cardiomyocytes. TRPC6 channels are involved in development of cardiac hypertrophy and related calcineurin-nuclear factor of activated T cells (NFAT) signaling. However, the exact location and roles of TRPC6 channels remain ill-defined in cardiomyocytes. We used an expression system based on neonatal rat ventricular myocytes (NRVMs) to investigate the location of TRPC6 channels and their role in calcium signaling. NRVMs isolated from 1- to 2-day-old animals were cultured and infected with an adenoviral vector to express enhanced-green fluorescent protein (eGFP) or TRPC6-eGFP. After 3 days, NRVMs were fixed, immunolabeled, and imaged with confocal and super-resolution microscopy to determine TRPC6 localization. Cytosolic calcium transients at 0.5 and 1 Hz pacing rates were recorded in NRVMs using indo-1, a ratio-metric calcium dye. Confocal and super-resolution microscopy suggested that TRPC6-eGFP localized to the sarcolemma. NRVMs infected with TRPC6-eGFP exhibited higher diastolic and systolic cytosolic calcium concentration as well as increased sarcoplasmic reticulum (SR) calcium load compared to eGFP infected cells. We applied a computer model comprising sarcolemmal TRPC6 current to explain our experimental findings. Altogether, our studies indicate that TRPC6 channels play a role in sarcolemmal and intracellular calcium signaling in cardiomyocytes. Our findings support the hypothesis that upregulation or activation of TRPC6 channels, e.g., in disease, leads to sustained elevation of the cytosolic calcium concentration, which is thought to activate calcineurin-NFAT signaling and cardiac hypertrophic remodeling. Also, our findings support the hypothesis that mechanosensitivity of TRPC6 channels modulates cytosolic calcium transients and SR calcium load.
Biometric From Surface Electromyogram (sEMG): Feasibility of User Verification and Identification Based on Gesture Recognition

Electrical biosignals are favored as biometric traits due to their hidden nature and allowing for liveness detection. This study explored the feasibility of surface electromyogram (sEMG), the electrical manifestation of muscle activities, as a biometric trait. The accurate gesture recognition from sEMG provided a unique advantage over two traditional electrical biosignal traits, electrocardiogram (ECG), and electroencephalogram (EEG), enabling users to customize their own gesture codes. The performance of 16 static wrist and hand gestures was systematically investigated in two identity management modes: verification and identification. The results showed that for a single fixed gesture, using only 0.8-second data, the averaged equal error rate (EER) for verification was 3.5%, and the averaged rank-1 for identification was 90.3%, both comparable to the reported performance of ECG and EEG. The function of customizing gesture code could further improve the verification performance to 1.1% EER. This work demonstrated the potential and effectiveness of sEMG as a biometric trait in user verification and identification, beneficial for the design of future biometric systems.
Emerging Methods for Enhancing Pluripotent Stem Cell Expansion

Pluripotent stem cells (PSCs) have great potential to revolutionize the fields of tissue engineering and regenerative medicine as well as stem cell therapeutics. However, the end goal of using PSCs for therapeutic use remains distant due to limitations in current PSC production. Conventional methods for PSC expansion have limited potential to be scaled up to produce the number of cells required for the end-goal of therapeutic use due to xenogenic components, high cost or low efficiency. In this mini review, we explore novel methods and emerging technologies of improving PSC expansion: the use of the two-dimensional mechanobiological strategies of topography and stiffness and the use of three-dimensional (3D) expansion methods including encapsulation, microcarrier-based culture, and suspension culture. Additionally, we discuss the limitations of conventional PSC expansion methods as well as the challenges in implementing non-conventional methods.
Probe Signal Values in mRNA Arrays Imply an Excessive Involvement of Neutrophil FCGR1 in Tuberculosis

The perturbed genes from transcriptomes are often presented in terms of relative expressions against control samples. However, the probe signal values (PSVs) of genes, implying protein abundances, are often ignored. Here, we explored the PSVs in tuberculosis (TB)-relevant signature genes. The signatures from Mycobacterium tuberculosis-infected THP-1 cells were defined as induced (TMtb-i, with a derived TMtb-iNet) and repressed (TMtb-r). The signature from human blood was defined as a pulmonary TB (PTB)-specific signature (PTBsig). The analysis showed that before infection, TMtb-i and TMtb-iNet had lower PSVs and TMtb-r genes had average PSVs. In the blood of healthy donors, PTBsig (divided into up-regulated PTBsigUp and down-regulated PTBsigDn) displayed average PSVs. This was partly due to masking by the cellular heterogeneity of blood; diverse PSVs were seen in constituent cell populations (CD4/8+ T, monocytes and neutrophils). Specifically, the PSVs of PTBsigUp in the neutrophils of healthy donors were higher (implying higher protein abundances), and much higher in the neutrophils of PTB (implying excessive protein abundances). Based on the PSV patterns of PTBsigUp in four cell populations, we identified three representative highly homologous genes (FCGR1A, FCGR1B, and the pseudogene FCGR1CP, which were often poorly distinguished), of which the summed PSVs were the highest in the neutrophils of PTB patients and healthy donors. The three genes were all up-regulated and responsive to chemotherapy in the blood of PTB, as validated in an RNA-seq-based analysis. This PSV-based study confirms the excessive involvement of neutrophil FCGR1 in PTB.