Adiponectin receptor 1 variants contribute to hypertrophic cardiomyopathy that can be reversed by rapamycin.

Abstract:

:Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic heart muscle disease characterized by hypertrophy with preserved or increased ejection fraction in the absence of secondary causes. However, recent studies have demonstrated that a substantial proportion of individuals with HCM also have comorbid diabetes mellitus (~10%). Whether genetic variants may contribute a combined phenotype of HCM and diabetes mellitus is not known. Here, using next-generation sequencing methods, we identified novel and ultrarare variants in adiponectin receptor 1 (ADIPOR1) as risk factors for HCM. Biochemical studies showed that ADIPOR1 variants dysregulate glucose and lipid metabolism and cause cardiac hypertrophy through the p38/mammalian target of rapamycin and/or extracellular signal-regulated kinase pathways. A transgenic mouse model expressing an ADIPOR1 variant displayed cardiomyopathy that recapitulated the cellular findings, and these features were rescued by rapamycin. Our results provide the first evidence that ADIPOR1 variants can cause HCM and provide new insights into ADIPOR1 regulation.

journal_name

Sci Adv

journal_title

Science advances

authors

Dhandapany PS,Kang S,Kashyap DK,Rajagopal R,Sundaresan NR,Singh R,Thangaraj K,Jayaprakash S,Manjunath CN,Shenthar J,Lebeche D

doi

10.1126/sciadv.abb3991

subject

Has Abstract

pub_date

2021-01-06 00:00:00

issue

2

issn

2375-2548

pii

7/2/eabb3991

journal_volume

7

pub_type

杂志文章
  • Regulation of chaperone function by coupled folding and oligomerization.

    abstract::The homotrimeric molecular chaperone Skp of Gram-negative bacteria facilitates the transport of outer membrane proteins across the periplasm. It has been unclear how its activity is modulated during its functional cycle. Here, we report an atomic-resolution characterization of the Escherichia coli Skp monomer-trimer t...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abc5822

    authors: Mas G,Burmann BM,Sharpe T,Claudi B,Bumann D,Hiller S

    更新日期:2020-10-21 00:00:00

  • Programming van der Waals interactions with complex symmetries into microparticles using liquid crystallinity.

    abstract::Asymmetric interactions such as entropic (e.g., encoded by nonspherical shapes) or surface forces (e.g., encoded by patterned surface chemistry or DNA hybridization) provide access to functional states of colloidal matter, but versatile approaches for engineering asymmetric van der Waals interactions have the potentia...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb1327

    authors: Fuster HA,Wang X,Wang X,Bukusoglu E,Spagnolie SE,Abbott NL

    更新日期:2020-06-19 00:00:00

  • Ocean heat drives rapid basal melt of the Totten Ice Shelf.

    abstract::Mass loss from the West Antarctic ice shelves and glaciers has been linked to basal melt by ocean heat flux. The Totten Ice Shelf in East Antarctica, which buttresses a marine-based ice sheet with a volume equivalent to at least 3.5 m of global sea-level rise, also experiences rapid basal melt, but the role of ocean f...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1601610

    authors: Rintoul SR,Silvano A,Pena-Molino B,van Wijk E,Rosenberg M,Greenbaum JS,Blankenship DD

    更新日期:2016-12-16 00:00:00

  • Impact of complex topology of porous media on phase separation of binary mixtures.

    abstract::Porous materials, which are characterized by the large surface area and percolated nature crucial for transport, play an important role in many technological applications including battery, ion exchange, catalysis, microelectronics, medical diagnosis, and oil recovery. Phase separation of a mixture in such a porous st...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aap9570

    authors: Shimizu R,Tanaka H

    更新日期:2017-12-22 00:00:00

  • Dynamic band structure measurement in the synthetic space.

    abstract::Band structure theory plays an essential role in exploring physics in both solid-state systems and photonics. Here, we demonstrate a direct experimental measurement of the dynamic band structure in a synthetic space including the frequency axis of light, realized in a ring resonator under near-resonant dynamic modulat...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abe4335

    authors: Li G,Zheng Y,Dutt A,Yu D,Shan Q,Liu S,Yuan L,Fan S,Chen X

    更新日期:2021-01-08 00:00:00

  • Intrinsic reconstruction of ice-I surfaces.

    abstract::Understanding the precise atomic structure of ice surfaces is critical for revealing the mechanisms of physical and chemical phenomena at the surfaces, such as ice growth, melting, and chemical reactions. Nevertheless, no conclusive structure has been established. In this study, noncontact atomic force microscopy was ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb7986

    authors: Kawakami N,Iwata K,Shiotari A,Sugimoto Y

    更新日期:2020-09-11 00:00:00

  • History of the solar nebula from meteorite paleomagnetism.

    abstract::We review recent advances in our understanding of magnetism in the solar nebula and protoplanetary disks (PPDs). We discuss the implications of theory, meteorite measurements, and astronomical observations for planetary formation and nebular evolution. Paleomagnetic measurements indicate the presence of fields of 0.54...

    journal_title:Science advances

    pub_type: 杂志文章,评审

    doi:10.1126/sciadv.aba5967

    authors: Weiss BP,Bai XN,Fu RR

    更新日期:2021-01-01 00:00:00

  • Lasting organ-level bone mechanoadaptation is unrelated to local strain.

    abstract::Bones adapt to mechanical forces according to strict principles predicting straight shape. Most bones are, however, paradoxically curved. To solve this paradox, we used computed tomography-based, four-dimensional imaging methods and computational analysis to monitor acute and chronic whole-bone shape adaptation and re...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aax8301

    authors: Javaheri B,Razi H,Gohin S,Wylie S,Chang YM,Salmon P,Lee PD,Pitsillides AA

    更新日期:2020-03-06 00:00:00

  • Wigner solid pinning modes tuned by fractional quantum Hall states of a nearby layer.

    abstract::We studied a bilayer system hosting two-dimensional electron systems (2DESs) in close proximity but isolated from one another by a thin barrier. One 2DES has low electron density and forms a Wigner solid (WS) at high magnetic fields. The other has much higher density and, in the same field, exhibits fractional quantum...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aao2848

    authors: Hatke AT,Deng H,Liu Y,Engel LW,Pfeiffer LN,West KW,Baldwin KW,Shayegan M

    更新日期:2019-03-15 00:00:00

  • A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules.

    abstract::Sister chromatid cohesion requires cohesin to act as a protein linker to hold chromatids together. How cohesin tethers chromatids remains poorly understood. We have used optical tweezers to visualize cohesin as it holds DNA molecules. We show that cohesin complexes tether DNAs in the presence of Scc2/Scc4 and ATP demo...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay6804

    authors: Gutierrez-Escribano P,Newton MD,Llauró A,Huber J,Tanasie L,Davy J,Aly I,Aramayo R,Montoya A,Kramer H,Stigler J,Rueda DS,Aragon L

    更新日期:2019-11-27 00:00:00

  • Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.

    abstract::Kv2.1 channels mediate cell death-enabling loss of cytosolic potassium in neurons following plasma membrane insertion at somatodendritic clusters. Overexpression of the carboxyl terminus (CT) of the cognate channel Kv2.2 is neuroprotective by disrupting Kv2.1 surface clusters. Here, we define a seven-amino acid declus...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz8110

    authors: Schulien AJ,Yeh CY,Orange BN,Pav OJ,Hopkins MP,Moutal A,Khanna R,Sun D,Justice JA,Aizenman E

    更新日期:2020-07-01 00:00:00

  • Multidimensional risk in a nonstationary climate: Joint probability of increasingly severe warm and dry conditions.

    abstract::We present a framework for quantifying the spatial and temporal co-occurrence of climate stresses in a nonstationary climate. We find that, globally, anthropogenic climate forcing has doubled the joint probability of years that are both warm and dry in the same location (relative to the 1961-1990 baseline). In additio...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aau3487

    authors: Sarhadi A,Ausín MC,Wiper MP,Touma D,Diffenbaugh NS

    更新日期:2018-11-28 00:00:00

  • Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells.

    abstract::The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo-electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, w...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay9572

    authors: Carter SD,Hampton CM,Langlois R,Melero R,Farino ZJ,Calderon MJ,Li W,Wallace CT,Tran NH,Grassucci RA,Siegmund SE,Pemberton J,Morgenstern TJ,Eisenman L,Aguilar JI,Greenberg NL,Levy ES,Yi E,Mitchell WG,Rice WJ,Wigge

    更新日期:2020-04-01 00:00:00

  • Stabilizers as a design tool for new forms of the Lechner-Hauke-Zoller annealer.

    abstract::In a recent paper, Lechner, Hauke, and Zoller (LHZ) described a means to translate a Hamiltonian of N spin-1/2 particles with "all-to-all" interactions into a larger physical lattice with only on-site energies and local parity constraints. LHZ used this mapping to propose a novel form of quantum annealing. We provide ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1601246

    authors: Rocchetto A,Benjamin SC,Li Y

    更新日期:2016-10-21 00:00:00

  • Tuning bad metal and non-Fermi liquid behavior in a Mott material: Rare-earth nickelate thin films.

    abstract::Resistances that exceed the Mott-Ioffe-Regel limit (known as bad metal behavior) and non-Fermi liquid behavior are ubiquitous features of the normal state of many strongly correlated materials. We establish the conditions that lead to bad metal and non-Fermi liquid phases in NdNiO3, which exhibits a prototype bandwidt...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1500797

    authors: Mikheev E,Hauser AJ,Himmetoglu B,Moreno NE,Janotti A,Van de Walle CG,Stemmer S

    更新日期:2015-11-06 00:00:00

  • Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in myofibroblast differentiation.

    abstract::Fibrosis, characterized by aberrant tissue scarring from activated myofibroblasts, is often untreatable. Although the extracellular matrix becomes increasingly stiff and fibrous during disease progression, how these physical cues affect myofibroblast differentiation in 3D is poorly understood. Here, we describe a mult...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb5069

    authors: Matera DL,DiLillo KM,Smith MR,Davidson CD,Parikh R,Said M,Wilke CA,Lombaert IM,Arnold KB,Moore BB,Baker BM

    更新日期:2020-09-09 00:00:00

  • Cellular response to moderate chromatin architectural defects promotes longevity.

    abstract::Changes in chromatin organization occur during aging. Overexpression of histones partially alleviates these changes and promotes longevity. We report that deletion of the histone H3-H4 minor locus HHT1-HHF1 extended the replicative life span of Saccharomyces cerevisiae. This longevity effect was mediated through TOR s...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aav1165

    authors: Yu R,Sun L,Sun Y,Han X,Qin L,Dang W

    更新日期:2019-07-10 00:00:00

  • Nanobubble-controlled nanofluidic transport.

    abstract::Nanofluidic platforms offering tunable material transport are applicable in biosensing, chemical detection, and filtration. Prior studies have achieved selective and controllable ion transport through electrical, optical, or chemical gating of complex nanostructures. Here, we mechanically control nanofluidic transport...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abd0126

    authors: Rabinowitz J,Whittier E,Liu Z,Jayant K,Frank J,Shepard K

    更新日期:2020-11-13 00:00:00

  • Charge localization and reentrant superconductivity in a quasi-ballistic InAs nanowire coupled to superconductors.

    abstract::A semiconductor nanowire with strong spin-orbit coupling in proximity to a superconductor is predicted to display Majorana edge states emerging under a properly oriented magnetic field. The experimental investigation of these exotic states requires assessing the one-dimensional (1D) character of the nanowire and under...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aav1235

    authors: Estrada Saldaña JC,Žitko R,Cleuziou JP,Lee EJH,Zannier V,Ercolani D,Sorba L,Aguado R,De Franceschi S

    更新日期:2019-07-05 00:00:00

  • Ancient DNA shows domestic horses were introduced in the southern Caucasus and Anatolia during the Bronze Age.

    abstract::Despite the important roles that horses have played in human history, particularly in the spread of languages and cultures, and correspondingly intensive research on this topic, the origin of domestic horses remains elusive. Several domestication centers have been hypothesized, but most of these have been invalidated ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb0030

    authors: Guimaraes S,Arbuckle BS,Peters J,Adcock SE,Buitenhuis H,Chazin H,Manaseryan N,Uerpmann HP,Grange T,Geigl EM

    更新日期:2020-09-16 00:00:00

  • A matricellular protein fibulin-4 is essential for the activation of lysyl oxidase.

    abstract::Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (Fbln4-/- ) have disrupted collagen and elastin fibers and die shortly after birth from aortic and diaphragmatic rupture. The function of fibulin-4 in ECM assembly, however, remains elusive. Here, we show...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abc1404

    authors: Noda K,Kitagawa K,Miki T,Horiguchi M,Akama TO,Taniguchi T,Taniguchi H,Takahashi K,Ogra Y,Mecham RP,Terajima M,Yamauchi M,Nakamura T

    更新日期:2020-11-25 00:00:00

  • Decoupling of microbial carbon, nitrogen, and phosphorus cycling in response to extreme temperature events.

    abstract::Predicted changes in the intensity and frequency of climate extremes urge a better mechanistic understanding of the stress response of microbially mediated carbon (C) and nutrient cycling processes. We analyzed the resistance and resilience of microbial C, nitrogen (N), and phosphorus (P) cycling processes and microbi...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1602781

    authors: Mooshammer M,Hofhansl F,Frank AH,Wanek W,Hämmerle I,Leitner S,Schnecker J,Wild B,Watzka M,Keiblinger KM,Zechmeister-Boltenstern S,Richter A

    更新日期:2017-05-03 00:00:00

  • The politics of zero-sum thinking: The relationship between political ideology and the belief that life is a zero-sum game.

    abstract::The tendency to see life as zero-sum exacerbates political conflicts. Six studies (N = 3223) examine the relationship between political ideology and zero-sum thinking: the belief that one party's gains can only be obtained at the expense of another party's losses. We find that both liberals and conservatives view life...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay3761

    authors: Davidai S,Ongis M

    更新日期:2019-12-18 00:00:00

  • Multiplexed whole-animal imaging with reversibly switchable optoacoustic proteins.

    abstract::We introduce two photochromic proteins for cell-specific in vivo optoacoustic (OA) imaging with signal unmixing in the temporal domain. We show highly sensitive, multiplexed visualization of T lymphocytes, bacteria, and tumors in the mouse body and brain. We developed machine learning-based software for commercial ima...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz6293

    authors: Mishra K,Stankevych M,Fuenzalida-Werner JP,Grassmann S,Gujrati V,Huang Y,Klemm U,Buchholz VR,Ntziachristos V,Stiel AC

    更新日期:2020-06-12 00:00:00

  • Accelerated evolution of a minimal 63-amino acid dual transcription factor.

    abstract::Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is one of the smallest known repressors (66 amino acids), and activators are typically much larger (e.g., λ cI, 237 amino acids). Previ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aba2728

    authors: Brödel AK,Rodrigues R,Jaramillo A,Isalan M

    更新日期:2020-06-10 00:00:00

  • FeSe quantum dots for in vivo multiphoton biomedical imaging.

    abstract::An immense demand in biomedical imaging is to develop efficient photoluminescent probes with high biocompatibility and quantum yield, as well as multiphoton absorption performance to improve penetration depth and spatial resolution. Here, iron selenide (FeSe) quantum dots (QDs) are reported to meet these criteria. The...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay0044

    authors: Kwon J,Jun SW,Choi SI,Mao X,Kim J,Koh EK,Kim YH,Kim SK,Hwang DY,Kim CS,Lee J

    更新日期:2019-12-06 00:00:00

  • Dislocation-driven growth of two-dimensional lateral quantum-well superlattices.

    abstract::The advent of two-dimensional (2D) materials has led to extensive studies of heterostructures for novel applications. 2D lateral multiheterojunctions and superlattices have been recently demonstrated, but the available growth methods can only produce features with widths in the micrometer or, at best, 100-nm scale and...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aap9096

    authors: Zhou W,Zhang YY,Chen J,Li D,Zhou J,Liu Z,Chisholm MF,Pantelides ST,Loh KP

    更新日期:2018-03-23 00:00:00

  • Are coral reefs victims of their own past success?

    abstract::As one of the most prolific and widespread reef builders, the staghorn coral Acropora holds a disproportionately large role in how coral reefs will respond to accelerating anthropogenic change. We show that although Acropora has a diverse history extended over the past 50 million years, it was not a dominant reef buil...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1500850

    authors: Renema W,Pandolfi JM,Kiessling W,Bosellini FR,Klaus JS,Korpanty C,Rosen BR,Santodomingo N,Wallace CC,Webster JM,Johnson KG

    更新日期:2016-04-22 00:00:00

  • Dual mode standoff imaging spectroscopy documents the painting process of the Lamb of God in the Ghent Altarpiece by J. and H. Van Eyck.

    abstract::The ongoing conservation treatment program of the Ghent Altarpiece by Hubert and Jan Van Eyck, one of the iconic paintings of the west, has revealed that the designs of the paintings were changed several times, first by the original artists, and then during later restorations. The central motif, The Lamb of God, repre...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb3379

    authors: Van der Snickt G,Dooley KA,Sanyova J,Dubois H,Delaney JK,Gifford EM,Legrand S,Laquiere N,Janssens K

    更新日期:2020-07-29 00:00:00

  • Sequence-encoded colloidal origami and microbot assemblies from patchy magnetic cubes.

    abstract::Colloidal-scale assemblies that reconfigure on demand may serve as the next generation of soft "microbots," artificial muscles, and other biomimetic devices. This requires the precise arrangement of particles into structures that are preprogrammed to reversibly change shape when actuated by external fields. The design...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1701108

    authors: Han K,Shields CW 4th,Diwakar NM,Bharti B,López GP,Velev OD

    更新日期:2017-08-04 00:00:00