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Base editing: a novel cure for severe combined immunodeficiency

Signal Transduction and Targeted Therapy 2023年第10期8卷 4433-4435页

作者： Teng-Cheong Ha Michael morgan Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannover30625Germany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannover30625Germany Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMA02115USA

In a recent Cell article,McAuley,Kohn et *** proof-of-principle of a promising gene therapy(GT)approach to correct the underlying genetic defect responsible for CD3δ-deficient severe combined immunodeficiency(SCID)using a CRISPR-cas.-derived adenine-base-editor(ABE).1 This ground-breaking and important study could impact future GTs for monogenic diseases by providing novel tailored therapeutic options(Fig.1).

关键词： immunodeficiency al. diseases

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Exploring ancestral phenotypes and evolutionary development of the mammalian middle ear based on Early Cretaceous Jehol mammals

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National Science Review 2021年第5期8卷 57-66页

作者： Fangyuan Mao Cunyu Liu morgan Hill Chase Andrew K.Smith Jin Meng Key Laboratory of Evolutionary Systematics of Vertebrates Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of Sciences cas.Center for Excellence in Life and Paleoenvironment Division of Paleontology American Museum of Natural History Beipiao Pterosaur Museum of China 5. Microscopy and Imaging Facility American Museum of Natural History Earth and Environmental Sciences Graduate CenterCity University of New York

We report a new Cretaceous multituberculate mammal with 3 D auditory bones preserved. Along with other fossil and extant mammals, the unequivocal auditory bones display features potentially representing ancestral phenotypes of the mammalian middle ear. These phenotypes show that the ectotympanic and the malleus-incus complex changed notably during their retreating from the dentary at various evolutionary stages and suggest convergent evolution of some features to extant mammals. In contrast, the incudomalleolar joint was conservative in having a braced hinge configuration, which narrows the morphological gap between the quadroarticular jaw joint of non-mammalian cynodonts and the incudomalleolar articulations of extant mammals. The saddle-shaped and abutting malleus-incus complexes in therians and monotremes, respectively, could have evolved from the braced hinge joint *** evolutionary changes recorded in the Mesozoic mammals are largely consistent with the middle ear morphogenesis during the ontogeny of extant mammals, supporting the relation between evolution and development.

关键词： Cretaceous Jehol Biota malleus-incus ectotympanic mammal evolution

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Mechanism of progressive broad deformation from oceanic transform valley to off-transform faulting and rifting

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The Innovation 2022年第1期3卷 62-70页

作者： Fan Zhang Jian Lin Zhiyuan Zhou Hongfeng Yang Jason P.morgan Key Laboratory of Ocean and Marginal Sea Geology South China Sea Institute of OceanologyInnovation Academy of South China Sea Ecology and Environmental EngineeringChinese Academy of SciencesGuangzhou 510301China Department of Ocean Science and Engineering Southern University of Science and TechnologyShenzhen 518055China Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) Guangzhou 511458China Department of Geology and Geophysics Woods Hole Oceanographic InstitutionWoods HoleMA 02543USA Earth System Science Programme The Chinese University of Hong KongShatinHong Kong 999077China

Oceanic transform faults(TFs)are commonly viewed as single,narrow strikeslip seismic faults that offset two mid-ocean ridge ***,broad zones of complex deformation are ubiquitous at ***,we propose a new conceptual model for the progressive deformation within broad zones at oceanic TFs through detailed morphological,seismic,and stress *** argue that,under across-transform extension due to a change in plate motion,plate deformation occurs first along high-angle transtensional faults(TTFs)within the transform ***-transform normal faults(ONFs)form when across-transform deviatoric extensional stresses exceed the yield strength of the adjacent oceanic *** further extension,these normal faults can develop into off-transform rift zones(ORZs),some of which can further develop into transform plate *** illustrate that such progressive complex deformation is an inherent feature of oceanic *** new conceptual model provides a unifying theory to explain the observed broad deformation at global transform systems.

关键词： oceanic valley seismic

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Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 713C and SARS-CoV-2 main protease

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3924-3933页

作者： Bo Qin Gregory B.Craven Pengjiao Hou Julian Chesti Xinran Lu Emma S.Child Rhodri M.L.morgan Wenchao Niu Lina Zhao Alan Armstrong David J.Mann Sheng Cui NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100076China Department of Life Sciences Imperial College LondonSouth Kensington CampusLondon SW72AZUK Department of Chemistry Imperial College LondonMolecular Sciences Research HubWhite City CampusWood LaneLondon W120BZUK cas.Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsUniversity of Chinese Academy of SciencesBeijing 100049China

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional *** of these proteases exhibit a similar fold and contain an essential catalytic cysteine,offering the opportunity to inhibit these enzymes with electrophilic small *** we describe the successful application of quantitative irreversible tethering(qIT)to identify acrylamide fragments that target the active site cysteine of the 3C protease(3Cpro)of Enterovirus 71,the causative agent of hand,foot and mouth disease in humans,altering the substrate binding ***,we re-purpose these hits towards the main protease(Mpro)of SARS-CoV-2 which shares the 3C-like fold and a similar active *** hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its *** demonstrate that targeting the active site cysteine of Mpro can have profound allosteric effects,distorting secondary structures to disrupt the active dimeric unit.

关键词： SARS-CoV-2 Protease inhibitors Covalent fragments Allosteric inhibition EV71

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Expression Profiling of Genes Associated with Cyanogenesis in Three cas.ava Cultivars Containing Varying Levels of Toxic Cyanogens

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American Journal of Plant Sciences 2013年第7期4卷 1533-1545页

作者： morgan Echeverry-Solarte Victor Ocas.o-Ramirez Annete Figueroa Eduardo González Dimuth Siritunga Department of Biology University of Puerto Rico Mayagüez Mayagüez USA.

Cyanogenic glycosides, linamarin and lotaustralin, are presents in all tissues of cas.ava (Manihot esculenta Crantz) except seeds and function as a deterrent for herbivores as well as the translocable form of reduced nitrogen. The genes involved in the cyanogenic pathway [CYP79D1/D2 (EC 1.14.13), linamarase (EC 3.***.1.21), α-hydroxynitrile lyase (HNL, acetone-cyanohydrin lyase. EC 4.***.2.37) and b-cyanoalanine synthase (β-cas. EC 4.***.1.9] have been identified and partially characterized. Our objective was to identify the differential expression pattern of these genes in leaves and roots of three cas.ava cultivars with varying levels of cyanogenic glucosides. The results show that the differential ex- pression of the genes between leaves and roots is consistent with leaves being the primary site of synthesize of cyano- genic glucosides, which are then translocated to the roots. In addition, the varietal difference for cyanogenic glucoside levels could be explained in part by the combinatorial effort of the synthesis in the leaves and the linamarase catabolic step in the roots. Cluster analysis suggests a coordinated expression between CYP79D1/D2 and β-cas.genes as well as linamarase and HNL genes, which is in agreement with the spatial separation within a cell of the site of linamarin syn- thesis (vacuolar) and its breakdown to cyanide (cell wall). Furthermore, cluster analysis for cultivar classification using its gene expression profile match with the reported cyanide levels comparatively for the three cultivars. This is the first study that evaluates the transcriptional activities of the genes involved in the cyanogenic glycoside metabolism using a systematic approach.

关键词： cas.ava Cyanogenic Glucoside Gene Expression Real Time PCR

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Opportunities to search for extraterrestrial intelligence with the FAST

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Research in Astronomy and Astrophysics 2020年第5期20卷 193-204页

作者： Di Li Vishal Gajjar Pei Wang Andrew Siemion Zhi-Song Zhang Hai-Yan Zhang You-Ling Yue Yan Zhu Cheng-Jin Jin Shi-Yu Li Sabrina Berger Bryan Brzycki Jeff Cobb Steve Croft Daniel Czech David DeBoer Julia DeMarines Jamie Drew J.Emilio Enriquez Nectaria Gizani Eric J.Korpela Howard Isaacson Matthew Lebofsky Brian Lacki David H.E.MacMahon morgan Nanez Chen-Hui Niu Xin Pei Danny C.Price Dan Werthimer Pete Worden Yunfan Gerry Zhang Tong-Jie Zhang FAST Collaboration cas.Key Laboratory of FAST National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Department of Astronomy University of California BerkeleyBerkeley CA 94720USA SETI Institute Mountain ViewCA 94043USA Department of Astrophysics/IMAPP Radboud UniversityNijmegenNetherlands University of Malta Institute of Space Sciences and AstronomyMalta Space Sciences Laboratory University of CaliforniaBerkeleyBerkeley CA 94720USA Breakthrough Initiatives NASA Research ParkMoffett Field CA 94043USA Hellenic Open University School of Science&TechnologyParodos AristotelousPerivola PatronGreece University of Southern Queensland QLD 4350Australia Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Centre for Astrophysics&Supercomputing Swinburne University of TechnologyHawthornVIC 3122Australia Department of Astronomy Beijing Normal UniversityBeijing 100875China Institute of Astronomical Science Dezhou UniversityDezhou 253023China

The discovery of ubiquitous habitable extrasolar planets,combined with revolutionary advances in instrumentation and observational capabilities,has ushered in a renaissance in the search for extraterrestrial intelligence(SETI).Large scale SETI activities are now underway at numerous international *** Five-hundred-meter Aperture Spherical radio Telescope(FAST)is the largest single-aperture radio telescope in the world,and is well positioned to conduct sensitive searches for radio emission indicative of *** is one of the five key science goals specified in the original FAST project plan.A collaboration with the Breakthrough Listen Initiative was initiated in 2016 with a joint statement signed both by *** Yan,the then director of National Astronomical Observatories,Chinese Academy of Sciences(NAOC),and *** Worden,Chairman of the Breakthrough Prize *** this paper,we highlight some of the unique features of FAST that will allow for novel SETI *** identify and describe three different signal types indicative of a technological source,namely,narrow band,wide-band artificially dispersed and modulated ***,we propose observations with FAST to achieve sensitivities never before *** nearby exoplanets,such as TESS targets,FAST will be sensitive to an EIRP of 1.9×1011 W,well within the reach of current human *** the Andromeda Galaxy,FAST will be able to detect any Kardashev type II or more advanced civilization there.

关键词： Search for Extraterrestrial Intelligence Five-hundred-meter Aperture Spherical radio Telescope

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