Abstract:
:Hypertrophic cardiomyopathy (HCM) is a heritable cardiovascular disorder that affects 1 in 500 people. A significant percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two early-onset HCM mutations, D239N and H251N, affect the molecular biomechanics of human β-cardiac myosin. We observed significant increases (20%-90%) in actin gliding velocity, intrinsic force, and ATPase activity in comparison to wild-type myosin. Moreover, for H251N, we found significantly lower binding affinity between the S1 and S2 domains of myosin, suggesting that this mutation may further increase hyper-contractility by releasing active motors. Unlike previous HCM mutations studied at the molecular level using human β-cardiac myosin, early-onset HCM mutations lead to significantly larger changes in the fundamental biomechanical parameters and show clear hyper-contractility.
journal_name
Cell Repjournal_title
Cell reportsauthors
Adhikari AS,Kooiker KB,Sarkar SS,Liu C,Bernstein D,Spudich JA,Ruppel KMdoi
10.1016/j.celrep.2016.11.040subject
Has Abstractpub_date
2016-12-13 00:00:00pages
2857-2864issue
11issn
2211-1247pii
S2211-1247(16)31598-4journal_volume
17pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Effector, but not naïve, T cells are activated by toll-like receptor-2 (TLR2) stimulation, leading to cytokine production and proliferation. We found that the differential response is attributable to the lack of expression of the adaptor protein TIRAP in naive T cells. TIRAP expression is induced upon T-cell receptor ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107911
更新日期:2020-07-21 00:00:00
abstract::Complex febrile seizures (FSs) lead to a high risk of intractable temporal lobe epilepsy during adulthood, yet the pathological process of complex FSs is largely unknown. Here, we demonstrate that activated microglia extensively associated with glutamatergic neuronal soma displace surrounding GABAergic presynapses in ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108346
更新日期:2020-11-03 00:00:00
abstract::At presynaptic active zones, exocytosis of neurotransmitter vesicles (SVs) is driven by SNARE complexes that recruit Syb2 and SNAP25. However, it remains unknown which SNAREs promote the secretion of neuronal proteins, including those essential for circuit development and experience-dependent plasticity. Here we demon...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.04.032
更新日期:2015-05-19 00:00:00
abstract::MicroRNAs (miRNAs) regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks b...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.031
更新日期:2016-01-12 00:00:00
abstract::There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ∼3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical in...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.10.018
更新日期:2015-11-17 00:00:00
abstract::53BP1 plays a central role in dictating DNA repair choice between non-homologous end joining (NHEJ) and homologous recombination (HR), which is important for the sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis) of BRCA1-deficient cancers. In this study, we show that FOXK1 associates with 53BP1 and regula...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108018
更新日期:2020-08-11 00:00:00
abstract::Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expre...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.08.075
更新日期:2017-09-19 00:00:00
abstract::Antimitotic agents, including Taxol, disrupt microtubule dynamics and cause a protracted mitotic arrest and subsequent cell death. Despite the broad utility of these drugs in breast cancer and other tumor types, clinical response remains variable. Tumor-associated macrophages (TAMs) suppress the duration of Taxol-indu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.03.038
更新日期:2017-04-04 00:00:00
abstract::The histone methyl transferase enhancer of zeste homolog 2 (EZH2) is a master transcriptional regulator involved in histone H3 lysine 27 trimethylation. We aimed to elucidate the precise post-translational regulations of EZH2 and their role in cancer pathogenesis. Here, we show that SET and MYND domain containing 2 (S...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.004
更新日期:2019-11-05 00:00:00
abstract::The newest classes of anti-diabetic agents include sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor (GLP1R) agonists. The SGLT2 inhibitor dapagliflozin reduces glucotoxicity by glycosuria but elevates glucagon secretion. The GLP1R agonist liraglutide inhibits glucagon; therefore, ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.07.009
更新日期:2019-08-06 00:00:00
abstract::Vitamin D (VD) is a known differentiating agent, but the role of VD receptor (VDR) is still incompletely described in acute myeloid leukemia (AML), whose treatment is based mostly on antimitotic chemotherapy. Here, we present an unexpected role of VDR in normal hematopoiesis and in leukemogenesis. Limited VDR expressi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.12.055
更新日期:2020-01-21 00:00:00
abstract::Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with Prader-Willi syndrome (PWS), a genetic obesity syndrome characterized by severe hyperphagia. We fou...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.018
更新日期:2018-03-27 00:00:00
abstract::The use of retinal organoids requires efficient differentiation from induced pluripotent stem cells (iPSCs). In this issue of Cell Reports, Wang et al. (2018) examine how the chromatin landscape after iPSC programming predicts their ability to differentiate into retinal tissue. ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.02.078
更新日期:2018-03-06 00:00:00
abstract::Angiogenesis is a highly regulated process essential for organ development and maintenance, and its deregulation contributes to inflammation, cardiac disorders, and cancer. The Ca2+/nuclear factor of activated T cells (NFAT) signaling pathway is central to endothelial cell angiogenic responses, and it is activated by ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.04.008
更新日期:2018-05-08 00:00:00
abstract::The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close prox...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.08.007
更新日期:2017-08-22 00:00:00
abstract::Expansions of microsatellite repeats are responsible for numerous hereditary diseases in humans, including myotonic dystrophy and Friedreich's ataxia. Whereas the length of an expandable repeat is the main factor determining disease inheritance, recent data point to genomic trans modifiers that can impact the likeliho...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.08.051
更新日期:2017-09-05 00:00:00
abstract::Desensitization, signaling, and trafficking of G-protein-coupled receptors (GPCRs) are critically regulated by multifunctional adaptor proteins, β-arrestins (βarrs). The two isoforms of βarrs (βarr1 and 2) share a high degree of sequence and structural similarity; still, however, they often mediate distinct functional...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.08.053
更新日期:2019-09-24 00:00:00
abstract::The rate of protein synthesis varies according to the mRNA sequence in ways that affect gene expression. Global analysis of translational pausing is now possible with ribosome profiling. Here, we revisit an earlier report that Shine-Dalgarno sequences are the major determinant of translational pausing in bacteria. Usi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.073
更新日期:2016-02-02 00:00:00
abstract::Complex interactions between immune cells are an important component in the induction of obesity. Here, we show that Il2rg-/-Rag2-/- mice lacking all lymphocytes are resistant to diet-induced obesity. Transplantation of bone marrow cells from Rag2-/- mice, which lack only acquired immune cells, into Il2rg-/-Rag2-/- mi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.06.016
更新日期:2019-07-02 00:00:00
abstract::CRISPR/Cas-based technologies have revolutionized genetic approaches to addressing a wide range of neurobiological questions. The ability of CRISPR/Cas to introduce mutations into target genes allows us to perform in vivo loss-of-function experiments without generating genetically engineered mice. However, the lack of...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.06.038
更新日期:2019-07-09 00:00:00
abstract::The quality of mitochondria in skeletal muscle is essential for maintaining metabolic homeostasis during adaptive stress responses. However, the precise control mechanism of muscle mitochondrial quality and its physiological impacts remain unclear. Here, we demonstrate that FUNDC1, a mediator of mitophagy, plays a cri...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.127
更新日期:2018-05-01 00:00:00
abstract::The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.02.041
更新日期:2017-03-07 00:00:00
abstract::The first cell fate choice of the preimplantation embryo generates the extraembryonic trophoblast and embryonic epiblast lineages. Embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) can be utilized to investigate molecular mechanisms of this first cell fate decision. It has been established that ESCs can be...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.04.040
更新日期:2017-05-09 00:00:00
abstract::Virus infection is sensed by pattern recognition receptors (PRRs) detecting virus nucleic acids and initiating an innate immune response. DNA-dependent protein kinase (DNA-PK) is a PRR that binds cytosolic DNA and is antagonized by vaccinia virus (VACV) protein C16. Here, VACV protein C4 is also shown to antagonize DN...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.10.034
更新日期:2018-11-13 00:00:00
abstract::Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in nutrient homeostasis. GIP receptor (GIPR) is constitutively internalized and returned to the plasma membrane, atypical behavior for a G-protein-coupled receptor (GPCR). GIP promotes GIPR downregulation from the plasma membrane by inh...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.11.050
更新日期:2016-12-13 00:00:00
abstract::After implantation, pluripotent epiblasts are converted to embryonic ectoderm through cell-cell interactions that significantly change the transcriptional and epigenetic networks. An entrée to understanding this vital developmental transition is the t(w5) mutation of the mouse t complex. This mutation produces highly ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.10.004
更新日期:2012-11-29 00:00:00
abstract::Recurrent copy-number alterations, mutations, and transcript fusions of the genes encoding CDKs/cyclins are characterized in >10,000 tumors. Genomic alterations of CDKs/cyclins are dominantly driven by copy number aberrations. In contrast to cell-cycle-related CDKs/cyclins, which are globally amplified, transcriptiona...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107884
更新日期:2020-07-14 00:00:00
abstract::During pregnancy, maternal regulatory T cells (Tregs) are important in establishing immune tolerance to invading fetal extravillous trophoblasts (EVTs). CD25HIFOXP3+ Tregs are found at high levels in decidual tissues and have been shown to suppress fetus-specific and nonspecific responses. However, limited data are av...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.109
更新日期:2019-05-28 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disease biochemically characterized by aberrant protein aggregation, including amyloid beta (Aβ) peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a mechanism impaired in AD. To investigate the role of autophagy in Aβ pathology in vivo, we cr...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.08.042
更新日期:2013-10-17 00:00:00
abstract::Recently developed brain stimulation techniques have significantly advanced our ability to manipulate the brain's function. However, stimulating specific neurons in a desired region without significant surgical invasion remains a challenge. Here, we demonstrate a neuron-specific and region-targeted neural excitation s...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108033
更新日期:2020-08-18 00:00:00