Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic microtubule destabilization of multiciliated choroid plexus epithelial cells during postnatal lifetime

Choroid plexus (ChP) epithelium is composed of specialized multiciliated cells. By using multiple microscopic techniques, biochemical approaches in various mutant mice and longitudinal analysis from mouse embryogenesis to aging, we show that ChP cilia are built on a gradient of events which are spatio-temporally regulated. We uncover that ChP cilia develop prenatally since early tissue morphogenesis, and proceeds as a multi-step process characterized by basal body multiplication and axoneme formation directly at the apical cellular compartment. Our data also show that choroid plexus cilia contain both primary and motile features. Remarkably, we demonstrate that ChP cilia undergo axoneme resorption, starting from early youth, through a tubulin destabilization process, which is primarily controlled by polyglutamylation levels and could be mitigated by the removal of the microtubule-severing enzyme spastin. Notably, we demonstrate that this phenotype is preserved in human samples.
A hepatitis B virus (HBV) sequence variation graph improves sequence alignment and sample-specific consensus sequence construction for genetic analysis of HBV

Hepatitis B virus (HBV) remains a global public health concern, with over 250 million individuals living with chronic HBV infection (CHB) and no curative therapy currently available. Viral diversity is associated with CHB pathogenesis and immunological control of infection. Improved methods to characterize the viral genome at both the population and intra-host level could aid drug development efforts. Conventionally, HBV sequencing data are aligned to a linear reference genome and only sequences capable of aligning to the reference are captured for analysis. Reference selection has additional consequences, including sample-specific ‘consensus’ sequence construction. It remains unclear how to select a reference from available sequences and whether a single reference is sufficient for genetic analyses. Using simulated short-read sequencing data generated from full-length publicly available HBV genome sequences and HBV sequencing data from a longitudinally sampled individual with CHB, we investigate alternative graph-based alignment approaches. We demonstrate that using a phylogenetically representative ‘genome graph’ for alignment, rather than linear reference sequences, avoids issues of reference ambiguity, improves alignment, and facilitates the construction of sample-specific consensus sequences genetically similar to an individual’s infection. Graph-based methods can therefore improve efforts to characterize the genetics of viral pathogens, including HBV, and may have broad implications in host pathogen research.
MARCH5-dependent NLRP3 ubiquitination is an essential step for NEK7 docking on the mitochondria

The NLRP3 inflammasome is a global immune-sensor that is activated by a repertoire of endogenous and exogenous stimuli. NLRP3 translocates to mitochondria but whether mitochondria involvement in the inflammasome assembly is unclear. Here, we show that the mitochondrial E3 ligase MARCH5 is a key regulator of NLRP3 inflammasome assembly. Myeloid cell-specific March5 conditional knockout (March5 cKO) mice exhibited an attenuated mortality rate upon LPS or Pseudomonas aeruginosa challenge. Macrophages derived from March5 cKO mice failed to secrete IL-1β and IL-18 after microbial infection. Mechanistically, MARCH5 interacts with the NACHT domain of NLRP3 and promotes K27-linked polyubiquitination of K324 and K430 residues of NLRP3. Ubiquitination-defective NLRP3 mutants neither bind to NEK7, nor form NLRP3 oligomers, but remain binding to MAVS. Accordingly, NLRP3 mutants led to abortive ASC speck formation and diminished IL-1β production. We propose that MARCH5-dependent NLRP3 ubiquitination creates a docking site for NEK7 binding, playing as a fundamental step-wise regulator on the mitochondria.
A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing

The proteolytic active sites of the 26S proteasome are sequestered within the catalytic chamber of its 20S core particle (CP). Access to this chamber is through a narrow channel defined by the outer α subunits. Free 20S CP is found in a latent state in which the N-termini of neighboring α subunits form a gate blocking access to the channel. Entry of substrates can be facilitated by the attachment of the activators or regulatory particles, which can rearrange the blocking α subunit N-terminal residues. In order to determine the specific physiological role of individual elements working in concert within the gate, we constructed a set of truncations or single-site mutations in each of the participating α N-terminal tails. We report herein that whereas only a few N-termini are important for maintaining a closed gate, all seven N-termini participate in the open gate. Specifically, an invariant tyrosine (Y) in each subunit forms a hydrogen bond with a conserved aspartate (D) in the N-terminal tail of its counterclockwise neighbor, with the exception of the α1-α2 pair leaving a gap in the ring circumference. A third residue (X) of this YD(X) motif aligns the open channel; specifically, the phenylalanine (F) at this position of the α2 subunit comes in direct contact with the translocating substrate. Consequently, deletion of this α2 N-terminal tail slows down proteolysis despite the appearance of an open gate state. We conclude that the YD(X) motif in N-terminal tail of α subunits plays an important role in gating the proteasome and in processing the substrate.
Angiopoietin-like 4 shapes the intrahepatic T-cell landscape via eIF2α signaling during steatohepatitis in diet-induced NAFLD

Adaptive T-cell immune response is essential in conferring protective immunity, a process requiring tight cellular homeostasis regulation. Pathological intrahepatic T-cell landscape has a role in NAFLD propagation; however, its activation remains unknown. To address this gap, we extensively characterized a novel diet-induced NAFLD murine model (LIDPAD) featuring key phenotypic and genetic attributes reflective of human NAFLD. Comparative transcriptomic-guided staging of human and murine NASH reinforced the robustness of LIDPAD in recapitulating critical transitory stages of human NAFLD. We found that angiopoietin-like 4 (Angptl4) shapes activation of the intrahepatic T-cell landscape through the modulation of eIF2α signaling during fibrosis. Single-immune cell analysis and hepatic transcriptomics during fibrosis, and kinase inhibitor screening confirmed that Angptl4 orchestrates the hyperactivation of intrahepatic adaptive immunity via eIF2α signaling. Consistently, immunoblocking of cAngplt4 reduces T-cell overactivation, delaying disease aggravation. Taken together, Angptl4 is a crucial determinant in shaping intrahepatic adaptive immunity during fibrosis in NAFLD.
Exosome-Based Multivalent Vaccine: Achieving Potent Immunization, Broadened Reactivity, and Strong T-Cell Responses with Nanograms of Proteins

The pandemic emergency has brought to light the need for a new generation of rapidly developed vaccines that induce longer-lasting, potent, and broader immune responses. While the mRNA vaccines played a critical role during the emergency in reducing SARS-CoV-2 hospitalization rates and deaths, more efficient approaches are needed. ABSTRACT Currently approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultralow-temperature storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed, which offer broader immunity but require significant time for development and the use of an adjuvant to boost the immune response. Here, exosomes were used to deliver a bivalent protein-based vaccine in which two independent viral proteins were used. Exosomes were engineered to express either SARS-CoV-2 delta spike (Stealth X-Spike [STX-S]) or the more conserved nucleocapsid (Stealth X-Nucleocapsid [STX-N]) protein on the surface. When administered as a single product (STX-S or STX-N) or in combination (STX-S+N), both STX-S and STX-N induced strong immunization with the production of potent humoral and cellular immune responses. Interestingly, these results were obtained with the administration of only nanograms of protein and without an adjuvant. In two independent animal models (mouse and rabbit), the administration of nanograms of the STX-S+N vaccine resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other variants of spike, and strong T-cell responses. Importantly, no competition of immune responses was observed, allowing the delivery of nucleocapsid with spike to offer improved SARS-CoV-2 immunity. These data show that the StealthX exosome platform has the enormous potential to revolutionize vaccinology by combining the advantages of mRNA and recombinant protein vaccines into a superior, rapidly generated, low-dose vaccine resulting in potent, broader immunity. IMPORTANCE The pandemic emergency has brought to light the need for a new generation of rapidly developed vaccines that induce longer-lasting, potent, and broader immune responses. While the mRNA vaccines played a critical role during the emergency in reducing SARS-CoV-2 hospitalization rates and deaths, more efficient approaches are needed. A multivalent, protein-based vaccine delivered by exosomes could meet this urgent need due to the high speed of development, manufacturability, and the ability to produce a strong antibody response, with neutralizing antibodies and a strong T-cell response able to broadly combat viral infection with a minimum number of injections.
Evidence for an RNAi-independent role of DICER-LIKE2 in conferring growth inhibition and basal antiviral resistance

Higher plants encode four DICER-LIKE (DCL) enzymes responsible for the production of small non-coding RNAs which function in RNA interference (RNAi). Different RNAi pathways in plants effect transposon silencing, antiviral defense and endogenous gene regulation. DCL2 acts genetically redundantly with DCL4 to confer basal antiviral defense, but in other settings, DCL2 has the opposite function of DCL4, at least in formal genetic terms. For example, knockout of DCL4 causes growth defects that are suppressed by inactivation of DCL2. Current models maintain that the biochemical basis of both of these effects is RNAi via DCL2-dependent small interfering RNAs (siRNAs). Here, we report that neither DCL2-mediated antiviral resistance nor growth defects can be explained by silencing effects of DCL2-dependent siRNAs. Both functions are defective in genetic backgrounds that maintain high levels of DCL2-dependent siRNAs, either through specific point mutations in DCL2 or simply by reducing DCL2 dosage in plants heterozygous for dcl2 knockout alleles. Intriguingly, however, all functions of DCL2 depend on it having some level of catalytic activity. We discuss this requirement for catalytic activity, but not for the resulting siRNAs, in the light of recent findings that reveal a function of DCL2 in activation of innate immunity in response to cytoplasmic double-stranded RNA.
Chitosan oligosaccharide induces plant resistance gene expression in Pinus massoniana

Chitosan oligosaccharides are the main degradation products from chitosan or chitin and have been reported to induce resistance to diseases in herbaceous plants like cucumber and Arabidopsis. Concomitantly, pine wilt disease is a devastating disease of conifer tree species. Here, we hypothesized that chitosan oligosaccharides induce plant resistance gene (PRG) expression in the woody plant Masson pine, Pinus massoniana. Chitosan oligosaccharides were inoculated into P. massoniana seedlings and the BGISEQ-500 platform was used to generate transcriptomes from chitosan oligosaccharide-treated P. massoniana and control seedlings. A total of 501 differentially expressed genes (DEGs) were identified by comparing the treatment and control groups. A total of 251 (50.1%) DEGs were up-regulated in the treatment relative to the control seedlings and 250 (49.9%) were down-regulated. Inoculation of chitosan oligosaccharide induced the expression of 31 PRGs in P. massoniana seedlings and the relative expression levels of six of the PRGs were verified by RT-qPCR. This is the first study to demonstrate that chitosan oligosaccharide induces the expression of PRGs in a tree species. These results provide important insights into the function of chitosan oligosaccharides and further the prospects of developing a chitosan oligosaccharide-based immune inducer for controlling pine wilt disease.
BMP suppresses WNT to integrate patterning of orthogonal body axes in adult planarians

Adult regeneration restores patterning of orthogonal body axes after damage in a post-embryonic context. Planarians regenerate using distinct body-wide signals primarily regulating each axis dimension: anteroposterior Wnts, dorsoventral BMP, and mediolateral Wnt5 and Slit determinants. How regeneration can consistently form perpendicular tissue axes without symmetry-breaking embryonic events is unknown, and could either occur using fully independent, or alternatively, integrated signals defining each dimension. Here, we report that the planarian dorsoventral regulator bmp4 suppresses the posterior determinant wnt1 to pattern the anteroposterior axis. Double-FISH identified distinct anteroposterior domains within dorsal midline muscle that express either bmp4 or wnt1. Homeostatic inhibition bmp4 and smad1 expanded the wnt1 expression anteriorly, while elevation of BMP signaling through nog1;nog2 RNAi reduced the wnt1 expression domain. BMP signal perturbation broadly affected anteroposterior identity as measured by expression of posterior Wnt pathway factors, without affecting head regionalization. Therefore, dorsal BMP signals broadly limit posterior identity. Furthermore, bmp4 RNAi caused medial expansion of the lateral determinant wnt5 and reduced expression of the medial regulator slit. Double RNAi of bmp4 and wnt5 resulted in lateral ectopic eye phenotypes, suggesting bmp4 acts upstream of wnt5 to pattern the mediolateral axis. Therefore, bmp4 acts at the top of a patterning hierarchy both to control dorsoventral information and also, through suppression of Wnt signals, to regulate anteroposterior and mediolateral identity. These results reveal that adult pattern formation involves integration of signals controlling individual orthogonal axes. Author Summary Systems that coordinate long-range communication across axes are likely critical for enabling tissue restoration in regenerative animals. While individual axis pathways have been identified, there is not yet an understanding of how signal integration allows repatterning across 3-dimensions. Here, we report an unanticipated linkage between anteroposterior, dorsoventral, and mediolateral systems in planarians through BMP signaling. We find that dorsally expressed BMP restricts posterior and lateral identity by suppressing distinct Wnt signals in adult planarians. These results demonstrate that orthogonal axis information is not fully independent and suggest a potentially ancient role of integrated axis patterning in generating stable 3-dimensional adult forms.
SEC-TMT facilitates quantitative differential analysis of protein interaction networks

The majority of cellular proteins interact with at least one partner or assemble into molecular-complexes to exert their function. This network of protein-protein interactions (PPIs) and the composition of macromolecular machines differ between cell types and physiological conditions. Therefore, characterizing PPI networks and their dynamic changes is vital for discovering novel biological functions and underlying mechanisms of cellular processes. However, producing an in-depth, global snapshot of PPIs from a given specimen requires measuring tens to thousands of LC-MS/MS runs. Consequently, while recent works made seminal contributions by mapping PPIs at great depth, almost all focused on just 1-2 conditions, generating comprehensive but mostly static PPI networks. In this study we report the development of SEC-TMT, a method that enables identifying and measuring PPIs in a quantitative manner from only 4-8 LC-MS/MS runs per biological sample. This was accomplished by incorporating tandem mass tag (TMT) multiplexing with a size exclusion chromatography mass spectrometry (SEC-MS) work-flow. SEC-TMT reduces measurement time by an order of magnitude while maintaining resolution and coverage of thousands of cellular interactions, equivalent to the gold standard in the field. We show that SEC-TMT provides benefits for conducting differential analyses to measure changes in the PPI network between conditions. This development makes it feasible to study dynamic systems at scale and holds the potential to drive more rapid discoveries of PPI impact on cellular processes.
Metal Forming Analysis

1. Mathematical background 2. Introduction to the finite element method 3. Finite elements for large deformation 4. Typical finite elements 5. Classification of finite element formulations 6. Auxiliary equations: contact, friction, incompressibility 7. Thermo-mechanical principles 8. Sheet metal formability tests 9. Steady state forming problems 10. Forging analysis 11. Sheet forming analysis 12. Recent research topics.
Formation kinetics of fractal nanofiber networks in organogels

The fractal structure of nanofiber networks formed in organogels is identified, using an in situ rheological method, together with a coupled supercritical fluid CO2 extraction/scanning electron microscopy technique. The rheological method allows us to have in-line measurements of the fractal growth of the nanofiber networks. In comparison with conventional light scattering techniques, the results obtained from this technique show much less scatter in data. Unlike conventional fractal aggregates, the growth of this type of fractal pattern is governed by a noncrystallographic branching mechanism, which occurs via self-mismatch nucleation and growth.
The relation of arithmetical ability to achievement in algebra and geometry

Is there sufficient relation between ability in arithmetic and achievement in algebra and geometry, when other factors are approximately equal, to justify a comprehensive review-course in arithmetic immediately preceding the beginning study of algebra and geometry ? School administrators and curriculum reconstructionists are frequently faced with this problem. Teachers of senior high school mathematics are asking if additional arithmetical ability would decrease the number of failures in high school mathematics. The method of attacking this problem was of a twofold nature; namely, (a) an examination of the opinions of authorities and a review of the findings of related investigations, and (b) a testing program in the high school department of Sue Bennett College, London, Kentucky. To determine the opinions of authorities, books on the teaching of mathematics (especially arithmetic, algebra, and geometry) and books dealing with mathematical subjects from the psychological point of view were examined. From the periodical files were collected the more recent treatments of the subject, including reports of surveys and investigations having to do with the inter-relationships of the three subjects. Theses, monographs, and reports of related investigations were reviewed.
A Robust SLAM For Highly Dynamic Environments

Simultaneous Localization and Mapping(SLAM) has broad applications such as driverless cars and indoor service robots. The SLAM techniques usually assume that environments are static, and it is difficult to obtain good accuracy in highly dynamic scenes. In this paper, we adopt the semantic segmentation method to filter out dynamic points according to prior knowledge. To avoid tracking failure due to insufficient feature points, epipolar geometry is used to retain potential dynamic points as much as possible. The proposed method is implemented based on the classical SLAM framework ORBSLAM2 and carried out experiments on the TUM RGBD datasets. Compared with ORBSLAM2, the localization accuracy of this algorithm is improved by 95% in highly dynamic environments.
Maneuvering target tracking from nautical radar images using particle-Kalman filters

In this paper, a new combined particle-Kalman filter (PF-KF)-based visual tracking approach is designed for maneuvering target tracking from X-band nautical radar images. Unlike existing target tracking approaches used by nautical radar, this approach incorporates a histogram-based visual tracking strategy to estimate the target position and velocity. It applies a sampling importance resampling (SIR) particle filter to obtain preliminary target positions, and then a Kalman filter to derive refined target position and velocity. A Bhattacharyya coefficient-based similarity function is employed to compare the reference target and candidate target models, which are constructed by a kernel-based histogram in radar images. An enhanced reference target model construction method that employs constant false alarm rate (CFAR) processing to enable automatic determination of reference region is proposed to improve the tracking stability and accuracy. Comparison of the target information obtained by the proposed PF-KF method from various field X-band nautical radar image sequences with those measured by GPS shows the proposed approach can provide a reliable and flexible online target tracking for nautical radar application. It is also shown that, in the scenario of strong sea clutter, the proposed approach outperforms the PF-only-based approach and the classical tracking approach which combines order-statistics (OS) CFAR processing and the Kalman filter.
An EEG Transfer Learning Algorithm Based on Mutual Information and Transfer Component Analysis

The Brain-Computer Interface (BCI) is the decoding of EEG signals from different users and conversion into required signal instructions. However, because different subjects produce different EEG signal distributions for the same signal, when taking the EEG data of a single subject into the trained classifier to classify the EEG signals of different subjects, the experimental accuracy is greatly reduced. In recent years, transfer learning (TL) has been applied in the field of brain-computer interfaces, and transfer learning can effectively reduce the difference in distribution between the two fields. In order to reduce the negative migration problem caused by the feature lengthiness of the transfer learning process. In this paper, a manifold spatial domain adaptive algorithm (M-TCA) based on mutual information feature selection is proposed. Firstly, the EEG data is preprocessed, the data is aligned in the manifold space, and the tangent features are obtained on the tangent plane of the SPD manifold after aligned data, and then the features are sorted and selected by mutual information algorithm, and finally the new source domain and target domain features are obtained by reducing the distribution distance between the source domain and the target domain by TCA algorithm. Experimental validation was performed on the BCI competition Ⅳ dataset 1 and compared with existing algorithm results. Experimental results show that the proposed M-TCA method has an average experimental accuracy of 71.23% of the single source domain on the BCI competition Ⅳ dataset1, which Compared with the existing experimental methods, it has certain advantages.