321 research outputs found

    MBD4 (methyl-CpG binding domain protein 4)

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    Review on MBD4 (methyl-CpG binding domain protein 4), with data on DNA, on the protein encoded, and where the gene is implicated

    Analysis of genetic diversity in Arrhenatherum elatius Germplasm using inter-simple sequence repeat (ISSR) markers

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    The genetic diversity of 19 Arrhenatherum elatius accessions was analyzed using 100 inter-simple sequence repeat (ISSR) primers, out of which 11 generated distinct amplification products. Out of the 152 total bands detected, 107 were polymorphic. The percentage of polymorphic bands (PPB) was 68.9% with an average of 9.73 polymorphic bands per primer. The ISSR-based genetic similarity (GS) coefficients among the 19 accessions ranged from 0.4821 to 0.7411, revealing high genetic diversity. Based on the UPGMA cluster analysis and the principal components analysis (PCA), the 19 A. elatius accessions were divided into three groups with similar situations. We found that the genetic distance was related to the geographical distance among the 19 A. elatius accessions studied. These results confirm the potential value of genetic diversity preservation for future breeding programs.Key words: Arrhenatherum elatius, genetic diversity, inter-simple sequence repeat (ISSR) markers

    Filming a live cell by scanning electrochemical microscopy: label-free imaging of the dynamic morphology in real time

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    The morphology of a live cell reflects the organization of the cytoskeleton and the healthy status of the cell. We established a label-free platform for monitoring the changing morphology of live cells in real time based on scanning electrochemical microscopy (SECM). The dynamic morphology of a live human bladder cancer cell (T24) was revealed by time-lapse SECM with dissolved oxygen in the medium solution as the redox mediator. Detailed local movements of cell membrane were presented by time-lapse cross section lines extracted from time-lapse SECM. Vivid dynamic morphology is presented by a movie made of time-lapse SECM images. The morphological change of the T24 cell by non-physiological temperature is in consistence with the morphological feature of early apoptosis. To obtain dynamic cellular morphology with other methods is difficult. The non-invasive nature of SECM combined with high resolution realized filming the movements of live cells

    Allogeneic hematopoietic stem cell transplantation in China: where we are and where to go

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    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and sometimes the only curative therapy for patients with certain hematological diseases. Allo-HSCT has been practiced in China for approximately 30 years, and great improvements have been made within the past decade, particularly in fields such as the haploidentical HSCT system, strategies to overcome relapse and GVHD, and modified HSCT for elderly patients. This review will describe the current situation and provide a prospective of these unique aspects of Allo-HSCT in China

    The Contrasting Effect of Macromolecular Crowding on Amyloid Fibril Formation

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    Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1) have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins.As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l.We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins) has been proposed

    The Role of Oligomerization and Cooperative Regulation in Protein Function: The Case of Tryptophan Synthase

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    The oligomerization/co-localization of protein complexes and their cooperative regulation in protein function is a key feature in many biological systems. The synergistic regulation in different subunits often enhances the functional properties of the multi-enzyme complex. The present study used molecular dynamics and Brownian dynamics simulations to study the effects of allostery, oligomerization and intermediate channeling on enhancing the protein function of tryptophan synthase (TRPS). TRPS uses a set of α/β–dimeric units to catalyze the last two steps of L-tryptophan biosynthesis, and the rate is remarkably slower in the isolated monomers. Our work shows that without their binding partner, the isolated monomers are stable and more rigid. The substrates can form fairly stable interactions with the protein in both forms when the protein reaches the final ligand–bound conformations. Our simulations also revealed that the α/β–dimeric unit stabilizes the substrate–protein conformation in the ligand binding process, which lowers the conformation transition barrier and helps the protein conformations shift from an open/inactive form to a closed/active form. Brownian dynamics simulations with a coarse-grained model illustrate how protein conformations affect substrate channeling. The results highlight the complex roles of protein oligomerization and the fine balance between rigidity and dynamics in protein function

    Generation of E-band metasurface-based vortex beam with reduced divergence angle

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    Vortex beams carrying orbital angular momentum (OAM) have attracted considerable attention for the development of high-capacity wireless communication systems due to their infinite sets of orthogonal modes. However, the practical applications of Laguerre-Gaussian type vortex beams are limited due to the fact that the divergence angle increases as the order of the OAM mode increases. In this work, we present metasurfaces that generate vortex beams carrying OAM modes with reduced divergence angles in the E-band frequency range. The metasurfaces were designed using eight different meta-atom phase elements, including a spiral phase distribution for OAM modes l=1 and 2, a phase gradient array to avoid interference with the source beam, and a lens pattern array to reduce the divergence angle. Through simulation and experimental measurement, it was confirmed that the divergence angle of the vortex beam generated by the metasurface with the lens pattern was reduced from 13 degrees to 9 degrees and 14 degrees to 11 degrees for OAM modes l=1 and 2, respectively, in comparison with the metasurface without the lens pattern. Our results provide new design methods for various applications based on OAM multiplexing especially in high frequency E-band range

    Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions

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    BackgroundTargeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing.ResultsAll panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden.ConclusionThis comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.Peer reviewe

    The muon system of the Daya Bay Reactor antineutrino experiment

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