Browsing by Author "Liu, Z."

Now showing 1 - 5 of 5

Open Access
Anticoagulant activity of singlet oxygen released from a water soluble endoperoxide by thermal cycloreversion
(Royal Society of Chemistry, 2021-04-19) Liu, M.; Uçar, Esma; Liu, Z.; Wang, L.; Yang, L.; Xu, J.; Akkaya, E. U.
Singlet oxygen generated by photosensitization has limited potential in vivo due to light attenuation in tissues. However, controlled chemical generation of this reactive oxygen species is likely to open new therapeutic spaces to explore. The fact that its activity is limited by the rate of cycloreversion reaction and the diffusion distance of the excited state molecular oxygen species, is a clear advantage, considering the serious side effects of off-target anticoagulants. In this work, we present novel 1,4-naphthalene endoperoxides as potential anti-coagulant agents due to thermal release of singlet oxygen.
Open Access
Control of LED emission with functional dielectric metasurfaces
(Wiley, 2020) Khaidarov, E.; Liu, Z.; Paniagua-Domínguez, R.; Ha, S. T.; Valuckas, V.; Liang, X.; Akimov, Y.; Bai, P.; Png, C. E.; Demir, Hilmi Volkan; Kuznetsov, A. I.
The improvement of light‐emitting diodes (LEDs) is one of the major goals of optoelectronics and photonics research. LED integration to complex photonic devices requires precise control of the wavefront of the emitted light. Metasurfaces are spatial arrangements of engineered scatters that may enable this light manipulation capability with unprecedented resolution. Most of these devices, however, are only able to function properly under irradiation of laser light with a large spatial coherence. LEDs, on the other hand, have angularly broad, Lambertian‐like emission patterns characterized by a low spatial coherence, which makes the integration of metasurface devices on LEDs challenging. A novel concept for metasurface integration on LED is proposed, using a cavity to increase the LED spatial coherence through an angular collimation. The experimental demonstration of the proposed concept is implemented on a GaP LED architecture including a hybrid metallic‐Bragg cavity. By integrating a silicon metasurface on top, two different functionalities of these compact devices are demonstrated: directional LED emission at a desired angle and LED emission of a vortex beam with an orbital angular momentum. The presented concept is general, being applicable to other incoherent light sources and enabling metasurfaces designed for plane waves to work with incoherent light emitters.
Open Access
DOT1L complex regulates transcriptional initiation in human erythroleukemic cells
(National Academy of Sciences, 2021-06-29) Wu, A.; Zhi, J.; Tian, T.; Cihan, A.; Cevher, Murat Alper; Liu, Z.; David, Y.; Muir, T. W.; Roeder, R. G.; Yu, M.
DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17, and ENL or AF9, is dysregulated in most cases of mixed-lineage leukemia (MLLr), and has been believed to regulate transcriptional elongation on the basis of its colocalization with RNA polymerase II (Pol II), the sharing of subunits (AF9 and ENL) between the DOT1L and super elongation complexes, and the distribution of H3K79 methylation on both promoters and transcribed regions of active genes. Here we show that DOT1L depletion in erythroleukemic cells reduces its global occupancy without affecting the traveling ratio or the elongation rate (assessed by 4sUDRB-seq) of Pol II, suggesting that DOT1L does not play a major role in elongation in these cells. In contrast, analyses of transcription initiation factor binding reveal that DOT1L and ENL depletions each result in reduced TATA binding protein (TBP) occupancies on thousands of genes. More importantly, DOT1L and ENL depletions concomitantly reduce TBP and Pol II occupancies on a significant fraction of direct (DOT1L-bound) target genes, indicating a role for the DOT1L complex in transcription initiation. Mechanistically, proteomic and biochemical studies suggest that the DOT1L complex may regulate transcriptional initiation by facilitating the recruitment or stabilization of transcription factor IID, likely in a monoubiquitinated H2B (H2Bub1)-enhanced manner. Additional studies show that DOT1L enhances H2Bub1 levels by limiting recruitment of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. These results advance our understanding of roles of the DOT1L complex in transcriptional regulation and have important implications for MLLr leukemias.
Open Access
Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
(American Association for the Advancement of Science (AAAS), 2022-12-20) Lee, D.; Pen, J. L.; Yatim, A.; Dong, B.; Aquino, Y.; Ogishi, M.; Pescarmona, R.; Talouarn, E.; Rinchai, D.; Zhang, P.; Perret, M.; Liu, Z.; Jordan, L.; Bozdemir, S. E.; Bayhan, G. I.; Beaufils, C.; Bizien, L.; Bisiaux, A.; Lei, W.; Hasan, M.; Chen, J.; Gaughan, C.; Asthana, A.; Libri, V.; Luna, Joseph M.; Jaffré, Fabrice; Hoffmann, H.; Michailidis, E.; Moreews, M.; Seeleuthner, Y.; Bilguvar, K.; Mane, S.; Flores, C.; Zhang, Y.; Arias, A. A.; Bailey, R.; Schlüter, A.; Milisavljevic, B.; Bigio, B.; Voyer, T. L.; Materna, M.; Gervais, A.; Moncada-Velez, M.; Pala, F.; Lazarov, T.; Levy, R.; Neehus, A.; Rosain, J.; Peel, J.; Chan, Y.; Morin, M.; Pino-Ramirez, R. M.; Belkaya, Serkan; Lorenzo, L.; Anton, J.; Delafontaine, S.; Toubiana, J.; Bajolle, F.; Fumadó, V.; DeDiego, M. L.; Fidouh, N.; Rozenberg, F.; Pérez-Tur, J.; Chen, S.; Evans, T.; Geissmann, F.; Lebon, P.; Weiss, S. R.; Bonnet, D.; Duval, X.; Cohort§, C.; Effort, C.; Pan-Hammarström, Q.; Planas, A. M.; Meyts, I.; Haerynck, F.; Pujol, A.; Sancho-Shimizu, V.; Dalgard, C.; Bustamante, J.; Puel, A.; Boisson-Dupuis, S.; Boisson, B.; Maniatis, T.; Zhang, Q.; Bastard, P.; Notarangelo, L.; Béziat, V.; Diego, R.; Rodriguez-Gallego, C.; Su, H. C.; Lifton, R. P.; Jouanguy, E.; Cobat, A.; Alsina, L.; Keles, S.; Haddad, E.; Abel, L.; Belot, A.; Quintana-Murci, L.; Rice, C. M.; Silverman, R. H.; Zhang, S.; Casanova, J.
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.
Open Access
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
(American Association for the Advancement of Science, 2020) Zhang, Q.; Liu, Z.; Moncada-Velez, M.; Chen, J.; Ogishi, M.; Bigio, B.; Yang, R.; Arias, A. A.; Zhou, Q.; Han, J. E.; Özçelik, Tayfun; Uğurbil, A. C.; Zhang, P.; Rapaport, F.; Li, J.; Spaan, A. N.
Clinical outcomes of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection range from silent infection to lethal coronavirus disease 2019 (COVID-19). Epidemiological studies have identified three risk factors for severe disease: being male, being elderly, and having other medical conditions. However, interindividual clinical variability remains huge in each demographic category. Discovering the root cause and detailed molecular, cellular, and tissue- and body-levelmechanismsunderlying life-threatening COVID-19 is of the utmost biological and medical importance.