Journal articles on the topic 'Asymmetric Cell Focusing'
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1
Özbey, Arzu, Mehrdad Karimzadehkhouei, Hossein Alijani, and Ali Koşar. "Microparticle Inertial Focusing in an Asymmetric Curved Microchannel." Fluids 3, no. 3 (August 9, 2018): 57. http://dx.doi.org/10.3390/fluids3030057.
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Inertial Microfluidics offer a high throughput, label-free, easy to design, and cost-effective solutions, and are a promising technique based on hydrodynamic forces (passive techniques) instead of external ones, which can be employed in the lab-on-a-chip and micro-total-analysis-systems for the focusing, manipulation, and separation of microparticles in chemical and biomedical applications. The current study focuses on the focusing behavior of the microparticles in an asymmetric curvilinear microchannel with curvature angle of 280°. For this purpose, the focusing behavior of the microparticles with three different diameters, representing cells with different sizes in the microchannel, was experimentally studied at flow rates from 400 to 2700 µL/min. In this regard, the width and position of the focusing band are carefully recorded for all of the particles in all of the flow rates. Moreover, the distance between the binary combinations of the microparticles is reported for each flow rate, along with the Reynolds number corresponding to the largest distances. Furthermore, the results of this study are compared with those of the microchannel with the same curvature angle but having a symmetric geometry. The microchannel proposed in this study can be used or further modified for cell separation applications.
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Stojanoska, Katerina, and Chen Shen. "Non-Hermitian planar elastic metasurface for unidirectional focusing of flexural waves." Applied Physics Letters 120, no. 24 (June 13, 2022): 241701. http://dx.doi.org/10.1063/5.0097177.
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Metasurfaces exhibiting spatially asymmetric inner structures have been shown to host unidirectional scattering effects, benefiting areas where directional control of waves is desired. In this work, we propose a non-Hermitian planar elastic metasurface to achieve unidirectional focusing of flexural waves. The unit cells are constructed by piezoelectric disks and metallic blocks that are asymmetrically loaded. A tunable material loss is then introduced by negative capacitance shunting. By suitably engineering the induced loss profile, a series of unit cells are designed, which can individually access the exceptional points manifested by unidirectional zero reflection. We then construct a planar metasurface by tuning the reflected phase to ensure constructive interference at one side of the metasurface. Unidirectional focusing of the incident waves is demonstrated, where the reflected wave energy is focused from one direction, and zero reflection is observed in the other direction. The proposed metasurface enriches the flexibility in asymmetric elastic wave manipulation as the loss and the reflected phase can be tailored independently in each unit cell.
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Balogh, Peter, and Prosenjit Bagchi. "The cell-free layer in simulated microvascular networks." Journal of Fluid Mechanics 864 (February 11, 2019): 768–806. http://dx.doi.org/10.1017/jfm.2019.45.
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In the microcirculation, a plasma layer forms near the vessel walls that is free of red blood cells (RBCs). This region, often termed as the cell-free layer (CFL), plays important haemorheological and biophysical roles, and has been the subject of extensive research. Many previous studies have considered the CFL development in single, isolated vessels that are straight tubes or channels, as well as in isolated bifurcations and mergers. In the body, blood vessels are typically winding and sequentially bifurcate into smaller vessels or merge to form larger vessels. Because of this geometric complexity, the CFL in vivo is three-dimensional (3D) and asymmetric, unlike in fully developed flow in straight tubes. The three-dimensionality of the CFL as it develops in a vascular network, and the underlying hydrodynamic mechanisms, are not well understood. Using a high-fidelity model of cellular-scale blood flow in microvascular networks with in vivo-like topologies, we present a detailed analysis of the fully 3D and asymmetric nature of the CFL in such networks. We show that the CFL significantly varies over different aspects of the networks. Along the vessel lengths, such variations are predominantly non-monotonic, which indicates that the CFL profiles do not simply become more symmetric over the length as they would in straight vessels. We show that vessel tortuosity causes the CFL to become more asymmetric along the length. We specifically identify a curvature-induced migration of the RBCs as the underlying mechanism of increased asymmetry in curved vessels. The vascular bifurcations and mergers are also seen to change the CFL profiles, and in the majority of them the CFL becomes more asymmetric. For most bifurcations, this is generally observed to occur such that the CFL downstream narrows on the side of the vessel nearest the upstream bifurcation, and widens on the other side. The 3D aspects of such behaviour are elucidated. For many bifurcations, a discrepancy exists between the CFL in the daughter vessels, which arises from a disproportionate partitioning between the flow rate and RBC flux. For most mergers, the downstream CFL narrows in the plane of the merger, but widens away from this plane. The dominant mechanism by which such changes occur is identified as the geometric focusing of the two merging streams. To our knowledge, this work provides the first simulation-based analysis of the 3D CFL structure in complex in vivo-like microvascular networks, including the hydrodynamic origins of the observed behaviour.
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Lu, Song-Yu, Amirreza Malekanfard, Shayesteh Beladi-Behbahani, Wuzhou Zu, Akshay Kale, Tzuen-Rong Tzeng, Yao-Nan Wang, and Xiangchun Xuan. "Passive Dielectrophoretic Focusing of Particles and Cells in Ratchet Microchannels." Micromachines 11, no. 5 (April 25, 2020): 451. http://dx.doi.org/10.3390/mi11050451.
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Focusing particles into a tight stream is critical for many microfluidic particle-handling devices such as flow cytometers and particle sorters. This work presents a fundamental study of the passive focusing of polystyrene particles in ratchet microchannels via direct current dielectrophoresis (DC DEP). We demonstrate using both experiments and simulation that particles achieve better focusing in a symmetric ratchet microchannel than in an asymmetric one, regardless of the particle movement direction in the latter. The particle focusing ratio, which is defined as the microchannel width over the particle stream width, is found to increase with an increase in particle size or electric field in the symmetric ratchet microchannel. Moreover, it exhibits an almost linear correlation with the number of ratchets, which can be explained by a theoretical formula that is obtained from a scaling analysis. In addition, we have demonstrated a DC dielectrophoretic focusing of yeast cells in the symmetric ratchet microchannel with minimal impact on the cell viability.
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Roeder, Ingo, Katrin Braesel, Ronny Lorenz, and Markus Loeffler. "Stem Cell Fate Analysis Revisited: Interpretation of Individual Clone Dynamics in the Light of a New Paradigm of Stem Cell Organization." Journal of Biomedicine and Biotechnology 2007 (2007): 1–9. http://dx.doi.org/10.1155/2007/84656.
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Many experimental findings on heterogeneity, flexibility, and plasticity of tissue stem cells are currently challenging stem cell concepts that assume a cell intrinsically predefined, unidirectional differentiation program. In contrast to these classical concepts, nonhierarchical self-organizing systems provide an elegant and comprehensive alternative to explain the experimental data. Here we present the application of such a self-organizing concept to quantitatively describe the hematopoietic stem cell system. Focusing on the analysis of individual-stem-cell fates and clonal dynamics, we particularly discuss implications of the theoretical results on the interpretation of experimental findings. We demonstrate that it is possible to understand hematopoietic stem cell organization without assumptions on unidirectional developmental hierarchies, preprogrammed asymmetric division events or other assumptions implying the existence of a predetermined stem cell entity. The proposed perspective, therefore, changes the general paradigm of thinking about stem cells.
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Vitali, Valerio, Rebecca Rothering, and Francesco Catania. "Fifty Generations of Amitosis: Tracing Asymmetric Allele Segregation in Polyploid Cells with Single-Cell DNA Sequencing." Microorganisms 9, no. 9 (September 17, 2021): 1979. http://dx.doi.org/10.3390/microorganisms9091979.
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Amitosis is a widespread form of unbalanced nuclear division whose biomedical and evolutionary significance remain unclear. Traditionally, insights into the genetics of amitosis have been gleaned by assessing the rate of phenotypic assortment. Though powerful, this experimental approach relies on the availability of phenotypic markers. Leveraging Paramecium tetraurelia, a unicellular eukaryote with nuclear dualism and a highly polyploid somatic nucleus, we probe the limits of single-cell whole-genome sequencing to study the consequences of amitosis. To this end, we first evaluate the suitability of single-cell sequencing to study the AT-rich genome of P. tetraurelia, focusing on common sources of genome representation bias. We then asked: can alternative rearrangements of a given locus eventually assort after a number of amitotic divisions? To address this question, we track somatic assortment of developmentally acquired Internal Eliminated Sequences (IESs) up to 50 amitotic divisions post self-fertilization. To further strengthen our observations, we contrast empirical estimates of IES retention levels with in silico predictions obtained through mathematical modeling. In agreement with theoretical expectations, our empirical findings are consistent with a mild increase in variation of IES retention levels across successive amitotic divisions of the macronucleus. The modest levels of somatic assortment in P. tetraurelia suggest that IESs retention levels are largely sculpted at the time of macronuclear development, and remain fairly stable during vegetative growth. In forgoing the requirement for phenotypic assortment, our approach can be applied to a wide variety of amitotic species and could facilitate the identification of environmental and genetic factors affecting amitosis.
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Ballarini, Francesca. "From DNA Radiation Damage to Cell Death: Theoretical Approaches." Journal of Nucleic Acids 2010 (2010): 1–8. http://dx.doi.org/10.4061/2010/350608.
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Some representative models of radiation-induced cell death, which is a crucial endpoint in radiobiology, were reviewed. The basic assumptions were identified, their consequences on predicted cell survival were analyzed, and the advantages and drawbacks of each approach were outlined. In addition to “historical” approaches such as the Target Theory, the Linear-Quadratic model, the Theory of Dual Radiation Action and Katz' model, the more recent Local Effect Model was discussed, focusing on its application in Carbon-ion hadrontherapy. Furthermore, a mechanistic model developed at the University of Pavia and based on the relationship between cell inactivation and chromosome aberrations was presented, together with recent results; the good agreement between model predictions and literature experimental data on different radiation types (photons, protons, alpha particles, and Carbon ions) supported the idea that asymmetric chromosome aberrations like dicentrics and rings play a fundamental role for cell death. Basing on these results, a reinterpretation of the TDRA was also proposed, identifying the TDRA “sublesions” and “lesions” as clustered DNA double-strand breaks and (lethal) chromosome aberrations, respectively.
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Hebiguchi, Miwa, Makoto Hirokawa, Yong-Mei Guo, Yoshinari Kawabata, Atsushi Komatsuda, Takehiko Sasaki, Yuichi Takakuwa, and Ken-ichi Sawada. "Enucleation of Human Erythroblasts Is a Process of Asymmetric Cytokinesis." Blood 108, no. 11 (November 16, 2006): 1663. http://dx.doi.org/10.1182/blood.v108.11.1663.1663.
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Abstract Background. During erythroblast enucleation, nuclei surrounded by plasma membrane separate from erythroblast cytoplasm. Enucleation has been thought to be a process similar to cytokinesis. However, more concrete evidence has been difficult to obtain because of a lack of an ex vivo experimental system capable of confirming cytokinesis. Focusing on the mechanism of cell division, we investigated the redistribution of cytoplasmic proteins and integral membrane proteins during enucleation, using ex vivo generation system of mature human blood cells from hematopoietic stem cells. Materials and Methods. The highly purified human CD34+ cells were grown in the presence of interleukin-3, stem cell factor and erythropoietin (EPO) in a liquid phase. After 7 days of culture, the generated cells (day 7 cells) were replaced in a medium with EPO alone. The cells matured and terminally differentiated into reticulocytes during a 13–15-day culture period. We mainly used non-gravity and non-pipetting system to avoid physical stress that may disrupt the connection between the nucleus and reticulocyte. Day 9 cells, predominantly consisted of polychromatophilic erythroblasts and expressed glycophorin A (GPA) at a purity of 97%, were labeled with DNA-staining dye SYTO21 for the direct monitoring of the enucleation process, using differential interference contrast microscopy. We also cultured day 9 cells until day 14, on 4-well culture slides or on the membrane of a cell culture insert system, and removed culture medium by aspiration without centrifugation and pipetting. The day 14 cells on the slide were analyzed using immunohistochemical staining, whereas the cells on the membrane were embedded in O.C.T. compound for confocal microscopy. Results. Approximately a half of erythroblasts enucleated until day 14. The monitoring of the enucleation process at day 13 showed autonomous extrusion of SYTO21 positive nucleus from single erythroblast. Some of the expelled nuclei were still connected with reticulocyte through strings that were positive for antibody against tubulin, actin, GPA, band 3 and glycophorin C (GPC). The expelled nuclei were covered by lamin, a protein specific for nuclear membrane, which were surrounded by a substance positive for GPA, band 3, GPC, p55, 4.1R80, actin, tubulin, b-spectrin, calnexin and cytochrome C, although the distribution of each proteins were asymmetric between nuclei and reticulocytes. An intense area of GPA, GPC, band 3, 4.1R80, actin, tubulin, myosin and b-spectrin was found in the region of the constriction between the extruding nucleus and incipient reticulocyte in enucleating cells. In cells just before enucleation, tubulin and actin formed a radial array around the nucleus. The center of the radial array was positive for centrin and NuMA, indicating that the cenriole formation occurred during an enucleation process. Conclusion. Our investigations show that a part of human erythroblasts enucleate independent of an interaction with accessory cells. The appearance of cenriole and the asymmetric redistribution of cytoplasmic and integral membrane proteins during enucleation strongly suggest that enucleation of human erythroblasts is a process of asymmetric cytokinesis.
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Dubreuil, R. R., T. K. Rosiere, M. C. Rosner, and G. B. Bouck. "Properties and topography of the major integral plasma membrane protein of a unicellular organism." Journal of Cell Biology 107, no. 1 (July 1, 1988): 191–200. http://dx.doi.org/10.1083/jcb.107.1.191.
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The cellular distribution, membrane orientation, and biochemical properties of the two major NaOH-insoluble (integral) plasma membrane proteins of Euglena are detailed. We present evidence which suggests that these two polypeptides (Mr 68 and 39 kD) are dimer and monomer of the same protein: (a) Antibodies directed against either the 68- or the 39-kD polypeptide bind to both 68- and 39-kD bands in Western blots. (b) Trypsin digests of the 68- and 39-kD polypeptides yield similar peptide fragments. (c) The 68- and 39-kD polypeptides interconvert during successive electrophoresis runs in the presence of SDS and beta-mercaptoethanol. (d) The 39-kD band is the only major integral membrane protein evident after isoelectric focusing in acrylamide gels. The apparent shift from 68 to 39 kD in focusing gels has been duplicated in denaturing SDS gels by adding ampholyte solutions directly to the protein samples. The membrane orientation of the 39-kD protein and its 68-kD dimer has been assessed by radioiodination in situ using intact cells or purified plasma membranes. Putative monomers and dimers are labeled only when the cytoplasmic side of the membrane is exposed. These results together with trypsin digestion data suggest that the 39-kD protein and its dimer have an asymmetric membrane orientation with a substantial cytoplasmic domain but with no detectable extracellular region. Immunolabeling of sectioned cells indicates that the plasma membrane is the only cellular membrane with significant amounts of 39-kD protein. No major 68- or 39-kD polypeptide bands are evident in SDS acrylamide gels or immunoblots of electrophoresed whole flagella or preparations enriched in flagellar membrane vesicles, nor is there a detectable shift in any flagellar polypeptide in the presence of ampholyte solutions. These findings are considered with respect to the well-known internal crystalline organization of the euglenoid plasma membrane and to the potential for these proteins to serve as anchors for membrane skeletal proteins.
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Watanabe, Nobuhisa, Takayuki Nagae, Yusuke Yamada, Ayana Tomita, Naohiro Matsugaki, and Masao Tabuchi. "Protein crystallography beamline BL2S1 at the Aichi synchrotron." Journal of Synchrotron Radiation 24, no. 1 (January 1, 2017): 338–43. http://dx.doi.org/10.1107/s1600577516018579.
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The protein crystallography beamline BL2S1, constructed at one of the 5 T superconducting bending-magnet ports of the Aichi synchrotron, is available to users associated with academic and industrial organizations. The beamline is mainly intended for use in X-ray diffraction measurements of single-crystals of macromolecules such as proteins and nucleic acids. Diffraction measurements for crystals of other materials are also possible, such as inorganic and organic compounds. BL2S1 covers the energy range 7–17 keV (1.8–0.7 Å) with an asymmetric-cut curved single-crystal monochromator [Ge(111) or Ge(220)], and a platinum-coated Si mirror is used for vertical focusing and as a higher-order cutoff filter. The beamline is equipped with a single-axis goniometer, a CCD detector, and an open-flow cryogenic sample cooler. High-pressure protein crystallography with a diamond anvil cell can also be performed using this beamline.
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Vallen, Elizabeth A., Juliane Caviston, and Erfei Bi. "Roles of Hof1p, Bni1p, Bnr1p, and Myo1p in Cytokinesis inSaccharomyces cerevisiae." Molecular Biology of the Cell 11, no. 2 (February 2000): 593–611. http://dx.doi.org/10.1091/mbc.11.2.593.
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Cytokinesis in Saccharomyces cerevisiae occurs by the concerted action of the actomyosin system and septum formation. Here we report on the roles of HOF1,BNI1, and BNR1 in cytokinesis, focusing on Hof1p. Deletion of HOF1 causes a temperature-sensitive defect in septum formation. A Hof1p ring forms on the mother side of the bud neck in G2/M, followed by the formation of a daughter-side ring. Around telophase, Hof1p is phosphorylated and the double rings merge into a single ring that contracts slightly and may colocalize with the actomyosin structure. Upon septum formation, Hof1p splits into two rings, disappearing upon cell separation. Hof1p localization is dependent on septins but not Myo1p. Synthetic lethality suggests that Bni1p and Myo1p belong to one functional pathway, whereas Hof1p and Bnr1p belong to another. These results suggest that Hof1p may function as an adapter linking the primary septum synthesis machinery to the actomyosin system. The formation of the actomyosin ring is not affected by bni1Δ, hof1Δ, orbnr1Δ. However, Myo1p contraction is affected bybni1Δ but not by hof1Δ orbnr1Δ. In bni1Δ cells that lack the actomyosin contraction, septum formation is often slow and asymmetric, suggesting that actomyosin contraction may provide directionality for efficient septum formation.
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Schmidt, Katharina, Mark-Alexander Schwarzbich, Nicola Lehners, Sivaramakrishna P. Rachakonda, Christine Falk, Anthony D. Ho, Peter Dreger, and Thomas Luft. "Prediction of Chronic Lung Graft-Versus-Host Disease By Angiopoietin-2." Blood 124, no. 21 (December 6, 2014): 1175. http://dx.doi.org/10.1182/blood.v124.21.1175.1175.
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Abstract Background: Severe chronic graft versus host disease (cGVHD) of the lung is a rare but often fatal complication of allogeneic stem cell transplantation (SCT). In order to identify patients at high risk of lung cGVHD prior to transplant, the aim of the present study was to test systematically candidate biomarkers for this purpose, thereby focusing on endothelial risk factors previously shown to be associated with the risk of refractory acute GVHD. These factors included angiopoietin-2 (ANG2), serum nitrates and asymmetric dimethylarginine (ADMA), as well as single nucleotide polymorphisms (SNPs) in the thrombomodulin gene (THBD). Methods: Patients were eligible if they were allo-grafted between June 2002 and December 2011 at our institution, and if their blood samples were available for nitrate, ANG2 and ADMA measurement at different landmarks (collected immediately before conditioning and on day +100 after allogeneic SCT). Concentrations of ANG2, ADMA and serum nitrates were quantified in patients’ sera by the multiplex protein array technology (Luminex). THBD SNP genotyping was performed using KASPar SNP Genotyping System v2.0 of K Bioscience in 384-well format. Cumulative incidence analysis of cause-specific hazards was performed. The occurrence of cGVHD was evaluated retrospectively by chart review applying clinical and histological criteria developed by the National Institute of Health’s consensus project (Filipovich et al., 2005). Results: Of a total sample of 329 eligible patients, 14 (4%) fulfilled the criteria for lung cGVHD. 19 out of 329 patients (6%) developed severe gastrointestinal cGVHD and 15 out of 329 patients (4%) developed sclerodermatous cGVHD. Elevated pre-transplant levels of ANG2 (> 1000 pg/ml) correlated with the incidence of lung cGVHD (p=0.037). In contrast, there was no association between pre-transplant levels of ANG2 and severe gastrointestinal cGVHD (p=0.684) or sclerodermatous cGVHD (p=0.242). Similarly, high ANG2 levels (> 4000 pg/ml) on day +100 after allogeneic SCT predicted lung cGVHD (p=0.009). Again, this effect was specific for lung cGVHD, as there was no association between high ANG2 levels on day +100 and sclerodermatous cGVHD (p=0.300) or severe gastrointestinal cGVHD (p=0.702). There was no correlation between lung cGVHD and antecedent acute GVHD (p=0.796). Moreover, no significant correlations between serum nitrates, ADMA and thrombomodulin-(THBD)-SNPs and the risk of lung cGVHD or any other manifestation of severe cGVHD could be identified. Conclusion: In contrast to other endothelial markers, elevated pretransplant and d +100 post-transplant ANG2 levels may be predictors of a high risk of lung cGVHD but not of gastrointestinal or sclerodermatous cGVHD. These preliminary results warrant validation by further studies. Moreover, this data suggests a different role of the endothelial component in the pathogenesis of acute vs chronic GVHD. Disclosures No relevant conflicts of interest to declare.
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Korczynska, Magdalena, Daniel Le, Elisabet Gregori-Puigjané, Noah Younger, Tobias Krojer, Anthony Tumber, Udo Oppermann, Danica Galonić Fujimori, and Brian Shoichet. "Virtual Screening of Histone Lysine Demethylase(JMJD2) identifies new inhibitors." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C820. http://dx.doi.org/10.1107/s2053273314091797.
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The JmjC domain-containing proteins are hydroxylases that confer posttranslational modifications on histone tails, by removing methylation marks on methylated lysine residues. This serves to either promote or repress gene transcription. The JMJD2A-D family members include the enzyme Jumonji domain 2C (JMJD2C), which specifically demethylates di- and trimethylated histone H3 at Lys 9 or Lys 36.[1] Dysregulation of JMJD2C has been implicated in prostate, colonic, and breast cancer as the demethylase can modify the expression levels of oncogenes.[2] The goal of the present study was to identify potent and selective small-molecule inhibitors of JMJD2C, to be used as chemical biology tools to further investigate the role of JMJD2C in cell proliferation and survival. Using high-resolution crystal structures of the JMJD2 subfamily members as templates, we have performed a small molecule virtual docking screen. From the ~3 million molecules that were docked, this experiment identified 21 compounds as possible leads. These compounds were tested against JMJD2C in enzymatic assays and here we report an overall hit rate of 76%, with 8 compounds demonstrating an IC50 of 176μM to 1.18μM. A molecule containing a salicylate core was selected as a candidate for optimization and thus far we have completed several rounds of iterative target-specific compound docking, hybrid molecule design, compound synthesis and in vitro characterization. Notably, our method demonstrated a substantial increase in potency when we linked two docked fragments together and further derivatized this new scaffold, through which we have successfully derived a 65nM inhibitor of JMJD2C. A compound representing the inhibitor scaffold has been co-crystallized with JMJD2A to a resolution of 2.4 Å. In the crystal structure each asymmetric unit contains two JMJD2A monomers, each bound to a single inhibitor molecule. This complex-structure superposes well with the docked pose for the hybrid series of compounds. We are now focusing our efforts on identifying an inhibitor that is selective for the JMJD2 family over other JmjC domain-containing proteins.
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Errington, Jeff. "From spores to antibiotics via the cell cycle." Microbiology 156, no. 1 (January 1, 2010): 1–13. http://dx.doi.org/10.1099/mic.0.035634-0.
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Spore formation in Bacillus subtilis is a superb experimental system with which to study some of the most fundamental problems of cellular development and differentiation. Work begun in the 1980s and ongoing today has led to an impressive understanding of the temporal and spatial regulation of sporulation, and the functions of many of the several hundred genes involved. Early in sporulation the cells divide in an unusual asymmetrical manner, to produce a small prespore cell and a much larger mother cell. Aside from developmental biology, this modified division has turned out to be a powerful system for investigation of cell cycle mechanisms, including the components of the division machine, how the machine is correctly positioned in the cell, and how division is coordinated with replication and segregation of the chromosome. Insights into these fundamental mechanisms have provided opportunities for the discovery and development of novel antibiotics. This review summarizes how the bacterial cell cycle field has developed over the last 20 or so years, focusing on opportunities emerging from the B. subtilis system.
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Frey, Carlos, Rafael Álvarez, Antonio Encina, and José Luis Acebes. "Tomato Graft Union Failure Is Associated with Alterations in Tissue Development and the Onset of Cell Wall Defense Responses." Agronomy 11, no. 6 (June 11, 2021): 1197. http://dx.doi.org/10.3390/agronomy11061197.
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Grafting is a technique applied to a considerable number of crops, with tomato standing out. However, this technique is limited by the obtaining of unfunctional grafts, which decrease the success rate and therefore the benefits achieved. The aim of this work was to analyze the failure in intraspecific grafting of tomato plants, focusing on tissue development, cell wall defense reactions, and the distribution of starch and soluble sugars at the graft junction. The success rate in autografts was higher than that of homografts and heterografts. Unfunctional homografts and heterografts showed similar responses: absence of vascular reconnections and lack of adhesion between scion and rootstock, even though callus cell clusters and differentiation of new vasculature were produced. The scions of unfunctional grafts accumulated more starch and soluble sugars than the rootstocks, showing a strong asymmetry in the response. In addition, three types of deposits were observed in the cell walls of unfunctional grafts: lignin, suberin, and callose, with the combined accumulation of more than one of them being frequent, particularly lignin and suberin. These deposits apparently prevent adhesion and seem to be a major cause of graft failure.
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Kim, Ki Hun, Jin Yong Kim, Myeong Ok Kim, and Myeong Hee Moon. "Two dimensional (pI & ds) separation of phosphorylated proteins by isoelectric focusing/asymmetrical flow field-flow fractionation: Application to prostatic cancer cell line." Journal of Proteomics 75, no. 8 (April 2012): 2297–305. http://dx.doi.org/10.1016/j.jprot.2012.01.034.
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McCaffery, P., M. O. Lee, M. A. Wagner, N. E. Sladek, and U. C. Drager. "Asymmetrical retinoic acid synthesis in the dorsoventral axis of the retina." Development 115, no. 2 (June 1, 1992): 371–82. http://dx.doi.org/10.1242/dev.115.2.371.
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An aldehyde dehydrogenase present at high levels in the dorsal retina of the embryonic and adult mouse was identified as the isoform AHD-2 known to oxidize retinaldehyde to retinoic acid. Comparative estimates of retinoic acid levels with a reporter cell line placed the retinas among the richest tissues in the entire body of the early embryo; levels in ventral retina, however, exceeded dorsal levels. Retinoic acid synthesis from retinaldehyde in the dorsal pathway was less effective than the ventral pathway at low substrate levels and more effective at high levels. The dorsal pathway was preferentially inhibited by disulfiram, while ventral synthesis was preferentially inhibited by p-hydroxymercuribenzoate. When protein fractions separated by isoelectric focusing were analyzed for retinoic acid synthesizing capacity by a zymography-bioassay, most of the synthesis in dorsal retina was found to be mediated by AHD-2, and ventral synthesis was mediated by dehydrogenase activities distinct in charge from AHD-2. Postnatally, levels of highest retinoic acid synthesis shifted from ventral to dorsal retina. In the adult retina, the dorsal pathway persisted, but the preferential ventral pathway was no longer detectable. Our observations raise the possibility that retinoic acid plays a role in the determination and maintenance of the dorsoventral axis of the retina, and that the morphogenetically significant asymmetry here lies in the spatial arrangement of synthetic pathways.
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Ghosh, Ritwik, Souvik Dubey, Subhankar Chatterjee, Biman Kanti Ray, and Julián Benito-León. "Mixed Upper and Lower Motor Neuron Damage in Japanese Encephalitis Virus Infection." Case Reports in Neurology 12, no. 3 (December 18, 2020): 482–88. http://dx.doi.org/10.1159/000510711.
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Cerebral manifestations in Japanese B encephalitis are well known. However, there are very few studies focusing on extra-cerebral manifestations, among which focal anterior horn cell involvement is exceedingly rare. We herein report a case of Japanese B encephalitis with focal anterior horn cell involvement and unfurl how stepwise clinical approach and targeted investigations helped to solve the diagnostic conundrum. A 27-year-old female was admitted with fever, headache, altered sensorium, and convulsions. She tested positive for Japanese B encephalitis-IgM. Following conservative management, she regained consciousness after 5 days when neurological examination revealed marked cognitive impairment, medial convergence of eyeballs, upward gaze restriction, upper limbs dystonia with brisk tendon jerks, and flaccid paraparesis. A repeat neurological examination, on day 15 of admission, showed marked wasting and intermittent fasciculation in both lower limbs. Brain magnetic resonance imaging showed asymmetrical (right > left) bilateral thalamic and midbrain lesions, hyperintense on T2 and T2-fluid-attenuated inversion recovery (FLAIR)-weighted imaging with mild diffusion restriction on diffusion-weighted imaging and apparent diffusion coefficient map, suggestive of encephalitis . Nerve conduction study revealed decreased compound muscle action potentials exclusively in lower limbs with intact sensory nerve action potentials. Electromyogram showed chronic denervation potentials and presence of spontaneous activity in lower limbs, but not in upper limbs, indicative of focal anterior horn cell involvement. Prognosis of Japanese B encephalitis does not only depend on cerebral sequelae. Anterior horn cell involvement can dictate poor outcome and can easily be missed if not carefully dealt with.
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Pollet, Hélène, Louise Conrard, Anne-Sophie Cloos, and Donatienne Tyteca. "Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?" Biomolecules 8, no. 3 (September 14, 2018): 94. http://dx.doi.org/10.3390/biom8030094.
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Extracellular vesicles (EVs) contribute to several pathophysiological processes and appear as emerging targets for disease diagnosis and therapy. However, successful translation from bench to bedside requires deeper understanding of EVs, in particular their diversity, composition, biogenesis and shedding mechanisms. In this review, we focus on plasma membrane-derived microvesicles (MVs), far less appreciated than exosomes. We integrate documented mechanisms involved in MV biogenesis and shedding, focusing on the red blood cell as a model. We then provide a perspective for the relevance of plasma membrane lipid composition and biophysical properties in microvesiculation on red blood cells but also platelets, immune and nervous cells as well as tumor cells. Although only a few data are available in this respect, most of them appear to converge to the idea that modulation of plasma membrane lipid content, transversal asymmetry and lateral heterogeneity in lipid domains may play a significant role in the vesiculation process. We suggest that lipid domains may represent platforms for inclusion/exclusion of membrane lipids and proteins into MVs and that MVs could originate from distinct domains during physiological processes and disease evolution.
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Schweizer, Riccardo, Wakako Tsuji, Vijay S. Gorantla, Kacey G. Marra, J. Peter Rubin, and Jan A. Plock. "The Role of Adipose-Derived Stem Cells in Breast Cancer Progression and Metastasis." Stem Cells International 2015 (2015): 1–17. http://dx.doi.org/10.1155/2015/120949.
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Conventional breast cancer extirpation involves resection of parts of or the whole gland, resulting in asymmetry and disfiguration. Given the unsatisfactory aesthetic outcomes, patients often desire postmastectomy reconstructive procedures. Autologous fat grafting has been proposed for reconstructive purposes for decades to restore form and anatomy after mastectomy. Fat has the inherent advantage of being autologous tissue and the most natural-appearing filler, but given its inconsistent engraftment and retention rates, it lacks reliability. Implementation of autologous fat grafts with cellular adjuncts, such as multipotent adipose-derived stem cells (ADSCs), has shown promising results. However, it is pertinent and critical to question whether these cells could promote any residual tumor cells to proliferate, differentiate, or metastasize or even inducede novocarcinogenesis. Thus far, preclinical and clinical study findings are discordant. A trend towards potential promotion of both breast cancer growth and invasion by ADSCs found in basic science studies was indeed not confirmed in clinical trials. Whether experimental findings eventually correlate with or will be predictive of clinical outcomes remains unclear. Herein, we aimed to concisely review current experimental findings on the interaction of mesenchymal stem cells and breast cancer, mainly focusing on ADSCs as a promising tool for regenerative medicine, and discuss the implications in clinical translation.
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Queller, David C. "Relatedness and the fraternal major transitions." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 355, no. 1403 (November 29, 2000): 1647–55. http://dx.doi.org/10.1098/rstb.2000.0727.
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Many of the major transitions in evolution involved the coalescence of independent lower–level units into a higher organismal level. This paper examines the role of kinship, focusing on the transitions to multicellularity in animals and to coloniality in insects. In both, kin selection based on high relatedness permitted cooperation and a reproductive division of labour. The higher relatedness of haplodiploid females to their sisters than to their offspring might not have been crucial in the origin of insect societies, and the transition to multicellularity shows that such special relationships are not required. When multicellular forms develop from a single cell, selfish conflict is minimal because each selfish mutant obtains only one generation of within–individual advantage in a chimaera. Conditionally expressed traits are particularly immune to within–individual selfishness because such mutations are rarely expressed in chimaeras. Such conditionally expressed altruism genes lead easily to the evolution of the soma, and the germ line might simply be what is left over. In most social insects, differences in relatedness ensure that there will be potential conflicts. Power asymmetries sometimes lead to such decisive settlements of conflicts that social insect colonies can be considered to be fully organismal.
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Moreira, Alvaro, Jamie Archambault, Dawn McDaniel, and Peter Hornsby. "2080." Journal of Clinical and Translational Science 1, S1 (September 2017): 55. http://dx.doi.org/10.1017/cts.2017.198.
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OBJECTIVES/SPECIFIC AIMS: To assess the efficacy of exogenous administration of MSCs in animal models of HIE. METHODS/STUDY POPULATION: Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed using MEDLINE, Web of Science, CINAHL, and Google Scholar. Search term items included mesenchymal stem/stromal cell, hypoxic ischemic encephalopathy, asphyxia, cerebral ischemia, and neonatology. We selected randomized and nonrandomized studies that examined in vivo neonatal models of induced HIE. We excluded studies that combined MSCs with an adjunct therapy. Data were collected on study specifics, MSC characteristics, and outcome measurements. The primary outcome was efficacy of MSC treatment, assessed by functional neurologic measures (cognitive, motor, sensory). Risk of bias was assessed using the SYRCLE’s risk of bias tool and we used the ARRIVE guidelines to describe the quality of study reporting. RESULTS/ANTICIPATED RESULTS: A total of 17 preclinical publications focusing on MSC therapy for HIE met our inclusion criteria. Fifteen of the studies (88%) induced HIE in rodents by ligating the common carotid artery followed by a period of hypoxic exposure. Nine (53%) studies derived their MSCs from rodent bone marrow, whereas the other investigators provided xenografts from human bone marrow or umbilical cord-derived MSCs. Range of MSC dose was between 0.25 and 3.5× 106 cells with 71% of the experiments transplanting the MSCs intranasally or intracerebral. Three studies (18%) administered multiple doses. The cylinder rearing test was the most common (73%) sensorimotor functional outcome performed in the first month following the establishment of HIE. All studies demonstrated a reduction in asymmetrical paw preference after receiving MSC therapy. Lesional size was assessed, using neuroimaging or histologic evaluations, and the majority of studies showed a decreased insult following MSC therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: MSC treatment demonstrates improved functional and structural outcomes that are encouraging for future translational studies.
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Gemenetzi, Katerina, Andreas Agathangelidis, Apostolia Papalexandri, Alejandro Medina, Elisa Genuardi, Theodoros Moysiadis, Evdoxia Hatjiharissi, et al. "Distinct Immunogenetic Signatures in IgA Versus IgG Multiple Myeloma." Blood 128, no. 22 (December 2, 2016): 2062. http://dx.doi.org/10.1182/blood.v128.22.2062.2062.
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Abstract Immunogenetic analysis of MM has proven instrumental in elucidating disease ontogeny e.g. by revealing the clonal relationship between switch variants expressed by the bone marrow plasma cells and myeloma progenitors in the marrow and blood; demonstrating the marked under-representation of the inherently autoreactive IGHV4-34 gene; and, identifying patterns of somatic hypermutation (SHM) indicative of post-germinal center derivation. Yet, limited information exists about the composition of the immunoglobulin (IG) gene repertoire in MM cases expressing different heavy chain isotype, in particular A versus G. This is relevant in light of studies showing an overall higher SHM impact in CD27+IgA+ compared to CD27+IgG+ normal memory B cells, perhaps reflecting a distinct location of the immune response, especially considering that IgA class switching mostly occurs in mucosa-associated lymphoid tissues. From a clinical perspective, it is also relevant to note that IgA patients exhibit a higher incidence of the t(4;14) translocation, shorter progression-free survival and worse median overall survival compared to IgG patients. Here, we explored potential differences in the immunoprofiles of IgA versus IgG MM focusing on IG gene repertoire and SHM characteristics. In total, 428 patients with a diagnosis of MM following the IMWG criteria from collaborating institutions in Greece, Italy and Spain (n=355) or retrieved from the LIGM-DB (n=73) were included in the study. Of these, 135 and 293 belonged to IgA and IgG MM groups, respectively. Amongst the evaluated productive IG rearrangements, IGHV3 subgroup genes predominated in both groups (IgA: 58.5%; IgG: 52.2%). However, at the individual gene level, major asymmetries were noted, since only 7 IGHV genes accounted for 41.6% of the IgA and 46.7% of the IgG cases, respectively. Of these, 3 genes were shared between IgA and IgG MM cases: IGHV3-30 (IgA: 11.9% - IgG: 13.3%), IGHV3-23 (IgA: 5.2% - IgG: 6.8%) and IGHV3-9 (IgA: 6.7% - IgG: 4.4%), whereas the remaining 4 of the 7 most frequent genes were specific for each group with significant (p<0.05) differences regarding the IGHV3-7 (5.2% in IgA versus 1.7% in IgG) and IGHV3-21 gene (0.7% in IgA 4.1% in IgG). IGHD3 predominated in both groups (IgA: 37% - IgG: 39.6%) followed by IGHD2 in IgG MM (18.4%) and IGHD6 in IgA MM (20.7%). IGHJ4 and IGHJ6 were the most frequent IGHJ genes with no significant differences in relative frequency. Searching for restricted IGHV-IGHJ combinations, we noted that the IGHV3-9 gene preferentially paired with the IGHJ6 gene in IgA MM versus the IGHJ4 gene in IgG MM (66.7% and 46.2% of all IGHV3-9 rearrangements, respectively). The median complementarity-determining region 3 (CDR3) length was identical in both IgA and IgG MM (15 amino acids, aa), yet differences were identified for specific CDR3 lengths as in the case of 19 aa, concerning 10.4% of all IgA versus 4.8% of all IgG rearrangements (p<0.05). Turning to SHM, the vast majority of rearrangements (IgA: 90.4%, IgG: 85%) were heavily mutated (IGHV germline identity (GI) <95%) with median GI of 91.8% for IgA and 92.2% for IgG. To study the topology of SHM, we compared the ratios of replacement (R) to silent (S) mutations in the framework (FR) and complementarity determining regions (CDRs) in cases expressing common frequent IGHV genes, namely IGHV3-23, IGHV3-30 and IGHV3-9 and identified distinct SHM patterns in all 3 instances: (i) IGHV3-23: the highest R/S ratios in IgA versus IgG MM were observed in FR2 (3.88) and CDR1 (3.9), respectively; (ii) IGHV3-30: overall "normal" SHM topology with higher R/S in CDRs rather than FRs, however, compared to IgG, IgA cases also showed a very high R/S in FR2 (5.3 versus 1.4); and, (iii) IGHV3-9: significantly (p<0.05) higher R/S ratios in CDR1 and CDR2 in IgG versus IgA cases (10.2 and 8.3 versus 1 and 2.9, respectively). Overall, in-depth immunogenetic analysis in the largest to-date series of IgA MM and IgG MM patients reveals differences regarding IGH gene repertoires, CDR3 characteristics and the topology of SHM. These findings suggest distinct antigen exposure histories and/or affinity maturation processes for IgA versus IgG MM, further highlighting the importance of microenvironmental stimuli in disease pathogenesis. Disclosures Terpos: Celgene: Honoraria; Novartis: Honoraria; Genesis: Consultancy, Honoraria, Other: Travel expenses; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel expenses, Research Funding. Stamatopoulos:Gilead: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria, Other: Travel expenses; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Other: Travel expenses, Research Funding.
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Nagao, Kohjiro, and Masato Umeda. "Cellular function of (a)symmetric biological membranes." Emerging Topics in Life Sciences, December 23, 2022. http://dx.doi.org/10.1042/etls20220029.
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In mammalian cells, phospholipids are asymmetrically distributed between the outer and inner leaflets of the plasma membrane. The maintenance of asymmetric phospholipid distribution has been demonstrated to be required for a wide range of cellular functions including cell division, cell migration, and signal transduction. However, we recently reported that asymmetric phospholipid distribution is disrupted in Drosophila cell membranes, and this unique phospholipid distribution leads to the formation of highly deformable cell membranes. In addition, it has become clear that asymmetry in the trans-bilayer distribution of phospholipids is disturbed even in living mammalian cells under certain circumstances. In this article, we introduce our recent studies while focusing on the trans-bilayer distribution of phospholipids, and discuss the cellular functions of (a)symmetric biological membranes.
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López-Aguirre, Camilo, Suzanne J. Hand, Daisuke Koyabu, Vuong Tan Tu, and Laura A. B. Wilson. "Prenatal Developmental Trajectories of Fluctuating Asymmetry in Bat Humeri." Frontiers in Cell and Developmental Biology 9 (May 26, 2021). http://dx.doi.org/10.3389/fcell.2021.639522.
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Fluctuating asymmetry (random fluctuations between the left and right sides of the body) has been interpreted as an index to quantify both the developmental instabilities and homeostatic capabilities of organisms, linking the phenotypic and genotypic aspects of morphogenesis. However, studying the ontogenesis of fluctuating asymmetry has been limited to mostly model organisms in postnatal stages, missing prenatal trajectories of asymmetry that could better elucidate decoupled developmental pathways controlling symmetric bone elongation and thickening. In this study, we quantified the presence and magnitude of asymmetry during the prenatal development of bats, focusing on the humerus, a highly specialized bone adapted in bats to perform under multiple functional demands. We deconstructed levels of asymmetry by measuring the longitudinal and cross-sectional asymmetry of the humerus using a combination of linear measurements and geometric morphometrics. We tested the presence of different types of asymmetry and calculated the magnitude of size-controlled fluctuating asymmetry to assess developmental instability. Statistical support for the presence of fluctuating asymmetry was found for both longitudinal and cross-sectional asymmetry, explaining on average 16% of asymmetric variation. Significant directional asymmetry accounted for less than 6.6% of asymmetric variation. Both measures of fluctuating asymmetry remained relatively stable throughout ontogeny, but cross-sectional asymmetry was significantly different across developmental stages. Finally, we did not find a correspondence between developmental patterns of longitudinal and cross-sectional asymmetry, indicating that processes promoting symmetrical bone elongation and thickening work independently. We suggest various functional pressures linked to newborn bats’ ecology associated with longitudinal (altricial flight capabilities) and cross-sectional (precocial clinging ability) developmental asymmetry differentially. We hypothesize that stable magnitudes of fluctuating asymmetry across development could indicate the presence of developmental mechanisms buffering developmental instability.
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Tang, Shuai, and Jianning Han. "Simulation study of acoustic refraction wave manipulation based on sub-wavelength artificial periodic structure." Modern Physics Letters B, November 5, 2020, 2150082. http://dx.doi.org/10.1142/s0217984921500822.
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We proposed a kind of unit cell composed of simple steel plate structures in this work. A variety of acoustic phenomena including anomalous refraction, asymmetric transmission, acoustic splitting and acoustic focusing were realized by coding the unit cells with different splicing modes. The transformation from plane acoustic wave to vortex acoustic wave was also realized by using the coding method of three-dimensional rotation. This work increased the functionality of the unit cell and provided a method for the design of sub-wavelength acoustic devices.
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Wang, Haiyang, Zhongyuan Pang, and Bo Zhu. "Independent Control of both Amplitude and Phase for Orthogonal Circularly Polarized Electromagnetic Waves through Polarization Conversions." Journal of Physics D: Applied Physics, November 3, 2022. http://dx.doi.org/10.1088/1361-6463/ac9fe0.
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Abstract Spin-selective multi-functional integrated metasurfaces have attracted much research attention due to its promising application prospects. However, the goal of independent and arbitrary control of both amplitude and phase for orthogonal circularly polarized waves still has not been achieved fully. This is because it requires mirror asymmetric structure to achieve such a goal but there is no apparent physical relation between the unit cell structure and the spin-selective properties. A simple method with clear physical pictures is proposed in this paper to achieve the goal of arbitrary spin-selective manipulations. The idea is to convert the incident orthogonal circularly polarized waves to orthogonal linearly polarized waves first, then manipulate the linearly polarized waves with matured techniques, and finally convert the linearly polarized waves back to the corresponding circularly polarized waves. Simulations and experiments have been carried out to validate the method. Using this idea, spin-selective focusing, spin-selective deflection and spin-selective orbital angular momentum vortex beam have been demonstrated.
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Honsho, Masanori, Shiro Mawatari, and Yukio Fujiki. "ATP8B2-Mediated Asymmetric Distribution of Plasmalogens Regulates Plasmalogen Homeostasis and Plays a Role in Intracellular Signaling." Frontiers in Molecular Biosciences 9 (June 27, 2022). http://dx.doi.org/10.3389/fmolb.2022.915457.
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Plasmalogens are a subclass of glycerophospholipid containing vinyl-ether bond at the sn-1 position of glycerol backbone. Ethanolamine-containing plasmalogens (plasmalogens) are major constituents of cellular membranes in mammalian cells and de novo synthesis of plasmalogens largely contributes to the homeostasis of plasmalogens. Plasmalogen biosynthesis is regulated by a feedback mechanism that senses the plasmalogen level in the inner leaflet of the plasma membrane and regulates the stability of fatty acyl-CoA reductase 1 (Far1), a rate-limiting enzyme for plasmalogen biosynthesis. However, the molecular mechanism underlying the localization of plasmalogens in cytoplasmic leaflet of plasma membrane remains unknown. To address this issue, we attempted to identify a potential transporter of plasmalogens from the outer to the inner leaflet of plasma membrane by focusing on phospholipid flippases, type-IV P-type adenosine triphosphatases (P4-ATPase), localized in the plasma membranes. We herein show that knockdown of ATP8B2 belonging to the class-1 P4-ATPase enhances localization of plasmalogens but not phosphatidylethanolamine in the extracellular leaflet and impairs plasmalogen-dependent degradation of Far1. Furthermore, phosphorylation of protein kinase B (AKT) is downregulated by lowering the expression of ATP8B2, which leads to suppression of cell growth. Taken together, these results suggest that enrichment of plasmalogens in the cytoplasmic leaflet of plasma membranes is mediated by ATP8B2 and this asymmetric distribution of plasmalogens is required for sensing plasmalogens as well as phosphorylation of AKT.
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Wu, Yu, Mo Li, and Mo Yang. "Post-Translational Modifications in Oocyte Maturation and Embryo Development." Frontiers in Cell and Developmental Biology 9 (June 2, 2021). http://dx.doi.org/10.3389/fcell.2021.645318.
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Mammalian oocyte maturation and embryo development are unique biological processes regulated by various modifications. Since de novo mRNA transcription is absent during oocyte meiosis, protein-level regulation, especially post-translational modification (PTM), is crucial. It is known that PTM plays key roles in diverse cellular events such as DNA damage response, chromosome condensation, and cytoskeletal organization during oocyte maturation and embryo development. However, most previous reviews on PTM in oocytes and embryos have only focused on studies of Xenopus laevis or Caenorhabditis elegans eggs. In this review, we will discuss the latest discoveries regarding PTM in mammalian oocytes maturation and embryo development, focusing on phosphorylation, ubiquitination, SUMOylation and Poly(ADP-ribosyl)ation (PARylation). Phosphorylation functions in chromosome condensation and spindle alignment by regulating histone H3, mitogen-activated protein kinases, and some other pathways during mammalian oocyte maturation. Ubiquitination is a three-step enzymatic cascade that facilitates the degradation of proteins, and numerous E3 ubiquitin ligases are involved in modifying substrates and thus regulating oocyte maturation, oocyte-sperm binding, and early embryo development. Through the reversible addition and removal of SUMO (small ubiquitin-related modifier) on lysine residues, SUMOylation affects the cell cycle and DNA damage response in oocytes. As an emerging PTM, PARlation has been shown to not only participate in DNA damage repair, but also mediate asymmetric division of oocyte meiosis. Each of these PTMs and external environments is versatile and contributes to distinct phases during oocyte maturation and embryo development.
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Morin, Gabriel, and Guillaume Canaud. "Treatment strategies for mosaic overgrowth syndromes of the PI3K-AKT-mTOR pathway." British Medical Bulletin, September 17, 2021. http://dx.doi.org/10.1093/bmb/ldab023.
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Abstract Introduction or background Mosaic overgrowth syndromes (OS) are a proteiform ensemble of rare diseases displaying asymmetric overgrowth involving any tissue type, with degrees of severity ranging from isolated malformation to life-threatening conditions such as pulmonary embolism. Despite discordant clinical presentations, all those syndromes share common genetic anomalies: somatic mutations of genes involved in cell growth and proliferation. The PI3K-AKT-mTOR signaling pathway is one of the most prominent regulators of cell homeostasis, and somatic oncogenic mutations affecting this pathway are responsible for mosaic OS. This review aims to describe the clinical and molecular characteristics of the main OS involving the PI3K-AKT-mTOR pathway, along with the treatments available or under development. Sources of data This review summarizes available data regarding OS in scientific articles published in peer-reviewed journals. Areas of agreement OS care requires a multidisciplinary approach relying on clinical and radiological follow-up along with symptomatic treatment. However, no specific treatment has yet shown efficacy in randomized control trials. Areas of controversy Clinical classifications of OS led to frequent misdiagnosis. Moreover, targeted therapies directed at causal mutated proteins are developing in OSs through cancer drugs repositioning, but the evidence of efficacy and tolerance is still lacking for most of them. Growing points The genetic landscape of OS is constantly widening and molecular classifications tend to increase the accuracy of diagnosis, opening opportunities for targeted therapies. Areas timely for developing research OS are a dynamic, expanding field of research. Studies focusing on the identification of genetic anomalies and their pharmacological inhibition are needed.
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Sedaghat, M., A. Amouye Foumani, and A. R. Niknam. "Controlling the characteristics of injected and accelerated electron bunch in corrugated plasma channel by temporally asymmetric laser pulses." Scientific Reports 12, no. 1 (May 17, 2022). http://dx.doi.org/10.1038/s41598-022-11955-6.
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AbstractIn laser-driven plasma wakefield accelerators, the accelerating electric field is orders of magnitude stronger than in conventional radio-frequency particle accelerators, but the dephasing between the ultrarelativistic electron bunch and the wakefield traveling at the group velocity of the laser pulse puts a limit on the energy gain. Quasi-phase-matching, enabled by corrugated plasma channels, is a technique for overcoming the dephasing limitation. The attainable energy and the final properties of accelerated electron beams are of utmost importance in laser wakefield acceleration (LWFA). In this work, using two-dimensional particle-in-cell simulations, the effect of the driving pulse duration on the performance of quasi-phase-matched laser wakefield acceleration (QPM-LWFA) is investigated. It is observed that for a pulse duration around half the plasma period, the maximum energy gain of the beam electrons finds its peak value. However, the results show that for a pulse of that duration the collimation of the bunch is much worse, compared to the case where the pulse duration is twice as long. Furthermore, the dynamics of the laser pulse and the evolution of the quality of the externally-injected electron bunch are studied for a symmetric pulse with sine-squared temporal profile, a positive skew pulse (i.e., one with sharp rise and slow fall), and a negative skew pulse (i.e., one with a slow rise and sharp fall). The results indicate that for a laser pulse with an appropriate pulse length compared with the plasma wavelength, the wakefield amplitude can be greatly enhanced by using a positive skew pulse, which leads to higher energy gain. Initially, this results from the stronger ponderomotive force associated with a fast rise time. Later, due to the distinct evolution of the three pulses with different initial profiles, the wakefield excited by the positive skew pulse becomes even stronger. In our simulations, the maximum energy gain for the asymmetric laser pulse with a fast rise time is almost two times larger than for the temporally symmetric laser pulse. Nevertheless, stronger focusing and defocusing fields are generated as well if a positive skew pulse is applied, which degrade the collimation of the bunch. These results should be taken into account in the design of miniature particle accelerators based on QPM-LWFA.
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"Cell Scientist to Watch – Eurico Morais-de-Sá." Journal of Cell Science 133, no. 23 (December 1, 2020): jcs256040. http://dx.doi.org/10.1242/jcs.256040.
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ABSTRACTEurico Morais-de-Sá graduated in biochemistry from the University of Porto, Portugal. After a research internship in protein crystallography at the Institute for Molecular and Cell Biology (IBMC) in Porto, Eurico moved to Cambridge, UK, to do his PhD with Daniel St Johnston at the Gurdon Institute. During this time, he studied cell polarity in the context of epithelial tissue and body-axis specification. In 2011, he was awarded EMBO and Marie Curie fellowships to return to Porto for his postdoctoral work with Claudio Sunkel at IBMC, where he used his cell polarity expertise to understand the regulatory processes of epithelial cell division. In 2018, Eurico established his own research group at Instituto de Inovação e Investigação em Saúde (i3S) focusing on the mechanisms by which epithelial cells modulate spatial asymmetry during cell division to maintain the function and integrity of proliferative tissues.
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Aladham, M. "P-231 Embryo morphokinetics in male factor infertility." Human Reproduction 37, Supplement_1 (June 29, 2022). http://dx.doi.org/10.1093/humrep/deac107.222.
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Abstract Study question Are embryo morphokinetics and division pattern susceptible to sperm origin? Summary answer Surgical retrieved sperm and Oligo-astheno-teratozoospermia have significant effect on morphokinetics and pattern of embryo development in IVF. What is known already Among couples seeking primary infertility treatment, approximately one third of them have male factor indication. Intracytoplasmic sperm injection (ICSI) has changed their prognosis to achieve successful pregnancy. Recently, there are many conflicting studies on the relation of sperm origin, embryo development and clinical outcome after fertilization burrier is passed by ICSI. Implementation of time-lapse monitoring system (TLM) allows us to analyze embryo development under stable conditions, and identify morphological, temporal, spatial parameters and cell cycle endpoints at which embryos with sperm of different origin exhibit distinct kinetics. The magnitude of variable morphokinetics in anticipating pregnancy outcome is not yet determined. Study design, size, duration This is a prospective cohort study that included 195 ICSI cycles stratified into three groups of different sperm origin (abnormal sperm (OAT), surgical sperm(SRS) and normosperm (CS)). Each group included around 400 zygotes for patients seeking IVF treatment in Fakih IVF/Dubai between December 2019 and December 2021 in Dubai / UAE. The mean age of patients is (22-40 years female/ 22-45 years male). Normospermia subset was limited to couples seeking gender selection and tubal factor. Participants/materials, setting, methods Embryo morphokinetics (time to polar body (tPB) until time to blastocyst (tB)) and cell cycle durations were analyzed. Embryos were examined for irregular cleavage phenotypes. The prevalence of each category of out of-range morphokinetics and abnormal cleavage among the different groups was compared. The portion of embryos displaying optimal ranges for the indicated morphokinetics was explored focusing on cell cycle duration. Finally, multi-variables influencing morphokinetics parameters were controlled. Chi2 test was performed in SPSS, P-value<0.05. Main results and the role of chance Embryos derived from SRS were later to reach tPNf and t2(26.66±9.16 and 29.03±8.52) than embryos derived from CS (25.15±4.20 and 27.84±4.98) and OAT (25.71±6.20 and 28.67±7.22). P < 0.05. Embryos derived from SRS reached t5(47.94±11.02) faster than both embryos derived from CS (49.61±8.89) and OAT (49.26±9.47). Embryos derived from SRS reached t6(51.64±10.44) faster than embryos from CS (53.10±8.96). P value=0.0. Embryos derived from SRS and OAT reached tSB (95.34±9.01 and 94.92 ±10.04) and tB(103.68±8.53 and 102.08±10.32) significantly later than embryos derived from CS (91.16±5.65 and 96.34±7.70). No correlation was found between sperm origin and irregular embryo phenotypes except for blastomere asymmetry and incomplete morulation. P = 0.0004. SRS and OAT had higher incidence of blastomere asymmetry at 2-, 3- and 4cell stage than CS. P = <0.05. For incomplete morulation, CS group had higher incidence of 1-3 fragments at morula stage(71.3%) than SRS and OAT (57.4% and 49%). However, OAT had higher incidence of 3-5 fragments at morula stage(35.9%) than SRS (224.1%) and CS (18.8%). Significantly, SRS displayed higher proportion of embryos out of range for most of the measured morphokinetics. P < 0.05. Accordingly, less proportion of embryos in SRS and OAT fall within optimal range for cell cycle duration P < 0.0. Antral follicle count, number of collected oocytes and male’s age had significantly affected morphokinetics and cleavage abnormality. Limitations, reasons for caution Selection of sperm by ICSI due to male- and severe male factor infertility may result in selecting live sperm with the best available normal morphology which may not reflect DNA fragmentation status of the overall sample where damage of DNA is more significant and lead to bias the results. Wider implications of the findings Embryo development potential with different sperm origin was compared based normal optimum morphokinetics or not. Further follow up study to investigate clinical outcome of implantation and clinical pregnancy rate, miscarriage rate and live birth rate is needed. Trial registration number DSREC-11/2021_07