The Mechanism of Tubular Recycling Endosome Biogenesis

Endocytic trafficking is a critical process for cellular homeostasis, and multiple ailments that include cardiovascular disease and cancer are related to the dysregulation of endocytic transport. As vesicles and target membranes are key to endocytic transport, lipids are essential for the regulation of endocytic trafficking pathways. We have shown that the tubular recycling endosomes (TRE) are essential for the regulation of endocytic recycling pathways. However, the mechanisms by which TRE are biosynthesized and carry out their functions remain unsolved. Studies from our lab have shown that phosphatidic acid (PA) recruits Molecule Interacting with Casl-Like protein 1 (MICAL-L1) as well as Syndapin2, and subsequently Eps15 homology domain containing protein EHD1 to the membrane of TREs as a complex, and this complex is essential for the biogenesis of TRE and efficient recycling of internalized receptors back to the plasma membrane. However, the involvement of PA in endocytic trafficking has not been well characterized. Diacylglycerol kinase (DGK) α is one of ten DGK isoforms that converts diacylglycerol (DAG) to PA. We showed that depletion of DGKα, a kinase devoid of a clathrin-dependent adaptor protein complex 2 binding site, results in an impaired biogenesis of TRE. As a consequence, we observed a delay in MHC I recycling to the plasma membrane. On the other hand, the rate of MHC I internalization remained unaffected. By Co-immunoprecipitation assay, we showed that DGKα forms a complex with the TRE hub protein, MICAL-L1. Given that MICAL-L1 and the F-BAR-containing membrane-tubulating protein Syndapin2 associate selectively with PA, whose generation is majorly mediated by DGKα, we propose a positive feedback loop in which DGKα generates PA to drive its own recruitment to TRE via its interaction with MICAL-L1. Our data support a novel role for the involvement of DGKα in TRE biogenesis and MHC I recycling. While the molecular mechanism of MICAL-L1 decorated TRE biogenesis is further revealed by our studies of the involvement of DGKα, major questions with regards to their function in endocytic recycling still remained unsolved, such as what cargos travel through these tubular membrane structures, where is the destination of these cargos, etc. We showed that TRE preferentially traffic cargos internalized via clathrin-independent endocytosis (CIE), and may originate from the sorting endosomes (SE). Since MICAL-L1 TRE is a major component of the endocytic recycling compartment (ERC), the understanding of the composition and cargo distribution within the ERC would further add to our knowledge of TRE functions. We used 3D Structured Illumination Microscopy, dual-channel and 3D direct Stochastic Optical Reconstruction Microscopy (dSTORM) to obtain new information about ERC morphology and cargo segregation. For the first time, we discovered that cargo internalized either via clathrin-mediated endocytosis (CME) or CIE remains segregated in the ERC, likely on distinct carriers. This suggests that no further sorting occurs upon cargo exit from SE. Moreover, 3D dSTORM data support a model in which some, but not all ERC vesicles are tethered by contiguous ‘membrane bridges’. These findings support a significantly altered model for endocytic recycling in mammalian cells, in which cargos are sorted in the peripheral endosomes and carried by MICAL-L1 decorated TRE to the ERC, while segregation is maintained at the ERC

Utjecaj dodatka ekstrakta maslačka, saharoze i starter kulture na viskoznost, sposobnost zadržavanja vode i pH jogurta

Dandelion extract is a traditional Chinese medicine and contains significant nutritional value. The aim of this study was to research the optimum fermentation conditions for dandelion addition to plain yogurt using a single factor experiments and orthogonal experiment. The results of the present study demonstrated that the addition of dandelion extract affected the viscosity, water-holding capacity and pH of yogurt. Optimized conditions for dandelion addition to plain yogurt based on viscosity, incubation time, pH and sensory score were 10 % sucrose, 0.3 % of the starter cultures, incubation time of 6.5 hours and 3 % dandelion extract. A new kind of dandelion yogurt with high viscosity, good water-holding capacity and good taste was prepared in this study.Ekstrakt maslačka je tradicionalni kineski lijek, a također ima i značajnu nutritivnu vrijednost. Cilj ovog istraživanja bio je ispitati optimalne uvjete fermentacije za dodavanje maslačka u jogurt korištenjem pojedinih faktorskih eksperimenata i ortogonalnog eksperimenta. Rezultati ove studije pokazali su da dodavanje ekstrakta maslačaka utječe na viskoznost, sposobnost zadržavanja vode i pH jogurta. Optimalni uvjeti za dodavanje maslačka u jogurt na temelju viskoznosti, vremena inkubacije, pH i senzorskog rezultata bili su 10 % saharoze, 0,3 % starter kulture, vrijeme inkubacije od 6,5 sati i dodatak 3 % ekstrakta maslačka. U ovoj studiji pripremljena je nova vrsta jogurta s dodatkom maslačka karakteriziranog visokom viskoznošću, dobrom sposobnošću zadržavanja vode i dobrim okusom

Rethinking Alignment in Video Super-Resolution Transformers

The alignment of adjacent frames is considered an essential operation in video super-resolution (VSR). Advanced VSR models, including the latest VSR Transformers, are generally equipped with well-designed alignment modules. However, the progress of the self-attention mechanism may violate this common sense. In this paper, we rethink the role of alignment in VSR Transformers and make several counter-intuitive observations. Our experiments show that: (i) VSR Transformers can directly utilize multi-frame information from unaligned videos, and (ii) existing alignment methods are sometimes harmful to VSR Transformers. These observations indicate that we can further improve the performance of VSR Transformers simply by removing the alignment module and adopting a larger attention window. Nevertheless, such designs will dramatically increase the computational burden, and cannot deal with large motions. Therefore, we propose a new and efficient alignment method called patch alignment, which aligns image patches instead of pixels. VSR Transformers equipped with patch alignment could demonstrate state-of-the-art performance on multiple benchmarks. Our work provides valuable insights on how multi-frame information is used in VSR and how to select alignment methods for different networks/datasets. Codes and models will be released at https://github.com/XPixelGroup/RethinkVSRAlignment.Comment: This paper has been accepted for NeurIPS 202

Extreme long-lifetime self-assembled monolayer for air-stable molecular junctions

The molecular electronic devices based on self-assembled monolayer (SAM) on metal surfaces demonstrate novel electronic functions for device minimization yet are unable to realize in practical applications, due to their instability against oxidation of the sulfur-metal bond. This paper describes an alternative to the thiolate anchoring group to form stable SAMs on gold by selenides anchoring group. Because of the formation of strong selenium-gold bonds, these stable SAMs allow us to incorporate them in molecular tunnel junctions to yield extremely stable junctions for over 200 days. A detailed structural characterization supported by spectroscopy and first-principles modeling shows that the oxidation process is much slower with the selenium-gold bond than the sulfur-gold bond, and the selenium-gold bond is strong enough to avoid bond breaking even when it is eventually oxidized. This proof of concept demonstrates that the extraordinarily stable SAMs derived from sel-enides are useful for long-lived molecular electronic devices and can possibly become important in many air-stable applications involving SAMs.</p

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

The impact of ageing mechanisms on musculoskeletal system diseases in the elderly

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future

Investigation of the Structure Requirement for 5-HT6 Binding Affinity of Arylsulfonyl Derivatives: A Computational Study

5-HT6 receptor has been implicated in a series of diseases including anxiety, depression, schizophrenia and cognitive dysfunctions. 5-HT6 ligands have been reported to play a significant role in the treatment for central nervous system (CNS) diseases. Presently, a large series of 223 5-HT6 ligands were studied using a combinational method by 3D-QSAR, molecular docking and molecular dynamics calculations for further improvement of potency. The optimal 3D models exhibit satisfying statistical results with r2ncv, q2 values of 0.85 and 0.50 for CoMFA, 0.81 and 0.53 for CoMSIA, respectively. Their predictive powers were validated by external test set, showing r2pred of 0.71 and 0.76. The contour maps also provide a visual representation of contributions of steric, electrostatic, hydrophobic and hydrogen bond fields as well as the prospective binding models. In addition, the agreement between 3D-QSAR, molecular docking and molecular dynamics simulation proves the rationality of the developed models. These results, we hope, may be helpful in designing novel and potential 5-HT6 ligands

A Multi-View Spatio-Temporal Feature Fusion Approach for Wind Turbine Condition Monitoring Based on SCADA Data

Condition monitoring of wind turbines is critical for increasing the reliability of the turbines and reducing their operation and maintenance costs. Supervisory control and data acquisition (SCADA) systems have been widely regarded as a promising technique to monitor the health status of turbines due to their abundance and cost-effective operation data. However, SCADA data are fundamentally multivariate time series with inherent spatio-temporal correlations. Therefore, it is still difficult to extract such correlations and then accurately identify the health status. This paper proposes a novel multi-view spatio-temporal feature fusion approach (MVSTCNN) based on convolutional neural networks (CNN) for condition monitoring of wind turbines. Specifically, multiple CNN modules with convolutional kernels of varying sizes are designed to extract correlations among several sensor variables and the temporal dependency concealed in each variable in parallel. A main advantage of the proposed method is its capacity to capture multiscale local information and global information simultaneously in both temporal and spatial dimensions, which improves the performance of condition monitoring. Real SCADA data from a wind farm is utilized to evaluate the effectiveness and superiority of the proposed approach. The SCADA data experiments demonstrate that the proposed approach is effective for early fault detection in wind turbines

3D printed nanocellulose-based label for fruit freshness keeping and visual monitoring

Food packaging systems with a single function of freshness keeping or monitoring may not be able to meet all practical needs. Herein, cellulose nanofibers (CNF)-based labels with dual functions of fruit freshness keeping and visual monitoring were prepared by coaxial 3D printing. CNF-based ink with blueberry anthocyanin was used to create the shell of fibers, exhibiting high formability and print fidelity as well as sensitive visual pH-responsiveness for freshness monitoring. Chitosan containing 1-methylcyclopropene (1-MCP) was loaded into the hollow microchannels of fibers, in which 1-MCP was trapped by the electrostatic effect of chitosan and CNF and exhibited a sustained release behavior. The 3D printed labels prolonged the shelf life of litchis for 6 days, meanwhile, they sensitively indicated the changes in freshness and the accuracy was confirmed by Headspace-Gas Chromatography-Ion Mobility Spectrometry. The CNF-based integrated labels developed in this work provided a new idea for the development of food intelligent packaging