Science

4 Nov 2022

Volume 378 | Issue 6619

Research Articles

1. Dual-polarity voltage imaging of the concurrent dynamics of multiple neuron types下载原文

First / Corresponding Author:

Madhuvanthi Kannan

Affiliations:

The John B. Pierce Laboratory, New Haven, CT 06519, USA.

Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.

Abstract:

Genetically encoded fluorescent voltage indicators are ideally suited to reveal the millisecond-scale interactions among and between targeted cell populations. However, current indicators lack the requisite sensitivity for in vivo multipopulation imaging. We describe next-generation green and red voltage sensors, Ace-mNeon2 and VARNAM2, and their reverse response-polarity variants pAce and pAceR. Our indicators enable 0.4- to 1-kilohertz voltage recordings from >50 spiking neurons per field of view in awake mice and ~30-minute continuous imaging in flies. Using dual-polarity multiplexed imaging, we uncovered brain state–dependent antagonism between neocortical somatostatin-expressing (SST+) and vasoactive intestinal peptide–expressing (VIP+) interneurons and contributions to hippocampal field potentials from cell ensembles with distinct axonal projections. By combining three mutually compatible indicators, we performed simultaneous triple-population imaging. These approaches will empower investigations of the dynamic interplay between neuronal subclasses at single-spike resolution.

2.Molecular basis of astrocyte diversity and morphology across the CNS in health and disease下载原文

First Author:

Fumito Endo①

Corresponding Author:

Baljit S. Khakh②

Affiliations:

Department of Physiology, University of California Los Angeles, Los Angeles, CA, USA.①②

Department of Neurobiology, University of California Los Angeles, Los Angeles, CA, USA.②

Abstract:

Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity. We identified gene networks correlated with astrocyte morphology, several of which unexpectedly contained Alzheimer’s disease (AD) risk genes. CRISPR/Cas9–mediated reduction of candidate genes reduced astrocyte morphological complexity and resulted in cognitive deficits. The same genes were down-regulated in human AD, in an AD mouse model that displayed reduced astrocyte morphology, and in other human brain disorders. We thus provide comprehensive molecular data on astrocyte diversity and mechanisms across the CNS and on the molecular basis of astrocyte morphology in health and disease.

3.Refactored genetic codes enable bidirectional genetic isolation下载原文

First Author:

Jerome F. Zurcher①

Corresponding Author:

Jason W. Chin②

Affiliations:

Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.①②

Abstract:

The near-universal genetic code defines the correspondence between codons in genes and amino acids in proteins. We refactored the structure of the genetic code inEscherichia coliand created orthogonal genetic codes that restrict the escape of synthetic genetic information into natural life. We developed orthogonal and mutually orthogonal horizontal gene transfer systems, which permit the transfer of genetic information between organisms that use the same genetic code but restrict the transfer of genetic information between organisms that use different genetic codes. Moreover, we showed that locking refactored codes into synthetic organisms completely blocks invasion by mobile genetic elements, including viruses, which carry their own translation factors and successfully invade organisms with canonical and compressed genetic codes.

4.On-demand cell-autonomous gene therapy for brain circuit disorders下载原文

First Author:

Yichen Qiu①

Corresponding Author:

Dimitri M. Kullmann②

Affiliations:

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.①②

Abstract:

Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and “healthy” surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.

5.Unprecedented fire activity above the Arctic Circle linked to rising temperatures下载原文

First/Corresponding Author:

Adria Descals

Affiliations:

CREAF, Centre de Recerca Ecològica i Aplicacions Forestals, Cerdanyola del Vallès, 08193 Barcelona, Catalonia, Spain.

CSIC, Global Ecology Unit CREAF-CSIC-UAB, Bellaterra, 08193 Barcelona, Catalonia, Spain.

Abstract:

Arctic fires can release large amounts of carbon from permafrost peatlands. Satellite observations reveal that fires burned ~4.7 million hectares in 2019 and 2020, accounting for 44% of the total burned area in the Siberian Arctic for the entire 1982–2020 period. The summer of 2020 was the warmest in four decades, with fires burning an unprecedentedly large area of carbon-rich soils. We show that factors of fire associated with temperature have increased in recent decades and identified a near-exponential relationship between these factors and annual burned area. Large fires in the Arctic are likely to recur with climatic warming before mid-century, because the temperature trend is reaching a threshold in which small increases in temperature are associated with exponential increases in the area burned.

6.Evidence for neutrino emission from the nearby active galaxy NGC 1068下载原文

First Author:

IceCube Collaboration

Abstract:

A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy’s active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of 79−20+22 neutrinos at tera–electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera–electron volt gamma rays from this source.

7.The control of carpel determinacy pathway leads to sex determination in cucurbits下载原文

First Author:

Siqi Zhang①

Corresponding Author: Abdelhafid Bendamane②

Affiliations:

Université Paris-Saclay, CNRS, INRAE, Université Evry, Institute of Plant Sciences Paris-Saclay (IPS2); 91190 Gif sur Yvette, France.①②

Abstract:

Male and female unisexual flowers evolved from hermaphroditic ancestors, and control of flower sex is useful for plant breeding. We isolated a female-to-male sex transition mutant in melon and identified the causal gene as the carpel identity geneCRABS CLAW (CRC). We show that the master regulator of sex determination in cucurbits, the transcription factorWIP1whose expression orchestrates male flower development, recruits the corepressor TOPLESS to theCRCpromoter to suppress its expression through histone deacetylation. Impairing TOPLESS-WIP1 physical interaction leads toCRCexpression, carpel determination, and consequently the expression of the stamina inhibitor, the aminocyclopropane-1-carboxylic acid synthase 7 (CmACS7), leading to female flower development. Our findings suggest that sex genes evolved to interfere with flower meristematic function, leading to unisexual flower development.

Reports

8.Molecular glue CELMoD compounds are regulators of cereblon conformation下载原文

First Author:

Edmond R. Watson①

Corresponding Author:

Gabriel C. Lander②

Affiliations:

Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA.①②

Abstract:

Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically relevant proteins for degradation. Prior crystallographic studies defined the drug-binding site within CRBN’s thalidomide-binding domain (TBD), but the allostery of drug-induced neosubstrate binding remains unclear. We performed cryo–electron microscopy analyses of the DNA damage-binding protein 1 (DDB1)–CRBN apo complex and compared these structures with DDB1-CRBN in the presence of CELMoD compounds alone and complexed with neosubstrates. Association of CELMoD compounds to the TBD is necessary and sufficient for triggering CRBN allosteric rearrangement from an open conformation to the canonical closed conformation. The neosubstrate Ikaros only stably associates with the closed CRBN conformation, illustrating the importance of allostery for CELMoD compound efficacy and informing structure-guided design strategies to improve therapeutic efficacy.

9.The January 2022 eruption of Hunga Tonga-Hunga Ha’apai volcano reached the mesosphere下载原文

First / Corresponding Author:

Simon R. Proud

Affiliations:

National Centre for Earth Observation, RAL Space, STFC Rutherford Appleton Laboratory, Harwell OX11, UK.

Atmospheric, Oceanic and Planetary Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.

Abstract:

Explosive volcanic eruptions can loft ash, gases, and water into the stratosphere, which affects both human activities and the climate. Using geostationary satellite images of the 15 January 2022 eruption of the Hunga Tonga-Hunga Ha’apai volcano, we find that the volcanic plume produced by this volcano reached an altitude of 57 kilometers at its highest extent. This places the plume in the lower mesosphere and provides observational evidence of a volcanic eruption injecting material through the stratosphere and directly into the mesosphere. We then discuss potential implications of this injection and suggest that the altitude reached by plumes from previous eruptions, such as the eruption of Mount Pinatubo in 1991, may have been underestimated because of a lack of observational data.

10.Robust multi-qubit quantum network node with integrated error detection下载原文

First Author:

P-J. Stas①

Corresponding Author:

M.D.Lukin②

Affiliation:

Department of Physics, Harvard University, Cambridge, MA 02138, USA.①②

Abstract:

Long-distance quantum communication and networking require quantum memory nodes with efficient optical interfaces and long memory times. We report the realization of an integrated two-qubit network node based on silicon-vacancy centers (SiVs) in diamond nanophotonic cavities. Our qubit register consists of the SiV electron spin acting as a communication qubit and the strongly coupled silicon-29 nuclear spin acting as a memory qubit with a quantum memory time exceeding 2 seconds. By using a highly strained SiV, we realize electron-photon entangling gates at temperatures up to 1.5 kelvin and nucleus-photon entangling gates up to 4.3 kelvin. We also demonstrate efficient error detection in nuclear spin–photon gates by using the electron spin as a flag qubit, making this platform a promising candidate for scalable quantum repeaters.

11.Multiple lineages of monkeypox virus detected in the United States, 2021–2022下载原文

First Author:

Crystal M. Gigante①

Corresponding Author:

Yu Li②

Affiliations:

National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.①②

Abstract:

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 US monkeypox cases: the major 2022 outbreak variant called B.1 and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.