Feynman’s clock, a new variational principle, and parallel-in-time quantum dynamics
Jarrod R. McClean, John A. Parkhill, and Alán Aspuru-Guzik
Methodology for studying quantum ground-state problems is currently more mature than what is available for quantum dynamical problems. Moreover, modern computing architectures demand that new algorithms be able to make use of parallel processing. We introduce a construction inspired by quantum computation that allows one to use virtually any model for a ground-state wavefunction to model quantum many-body dynamics and formulate it in a way that naturally leads to a parallel-in-time algorithm. We show (pp. E3901–E3909) how the elementary ground-state variational principle maps onto a new time-dependent variational principle and demonstrate practical examples of its use.
Nrf2 acts cell-autonomously in endothelium to regulate tip cell formation and vascular branching
Yanhong Wei, Junsong Gong, Rajesh K. Thimmulappa, Beata Kosmider, Shyam Biswal, and Elia J. Duh
Angiogenesis, in which new blood vessels form via endothelial cell (EC) sprouting from existing vessels, is critical in embryonic development and multiple disease processes. The intracellular molecular mechanisms governing sprouting angiogenesis remain incompletely understood. We found (pp. E3910–E3918) that transcription factor NF-E2–related factor 2 (Nrf2), well-known for regulating the stress response in multiple pathologic settings, is a critical intracellular regulator in ECs for sprouting angiogenesis in vascular development through delta-like 4 (Dll4)/Notch signaling. Understanding the molecular mechanisms by which Nrf2 regulates angiogenesis could facilitate therapeutic strategies targeting Nrf2 to treat angiogenesis-related diseases, including tumorigenesis, proliferative diabetic retinopathy, atherosclerosis, and ischemic disorders.
Irx3 and Pax6 establish differential competence for Shh-mediated induction of GABAergic and glutamatergic neurons of the thalamus
Ellen Robertshaw, Ken Matsumoto, Andrew Lumsden, and Clemens Kiecker
Classic embryological studies suggested that small groups of cells called organizers change the fate of neighboring tissues through inductive processes. In these studies it was also postulated that the receiving tissue has to be “competent” to respond to the inducer in a specific way. In the posterior forebrain, the signaling factor Sonic hedgehog is released from an organizer called the zona limitans intrathalamica and induces GABAergic and glutamatergic neurons of the thalamus. Here (pp. E3919–E3926) we demonstrate that the differential expression of two transcription factors, Irx3 and Pax6, spatially limits the area of competence for these inductions.
Epigenetic control of natural killer cell maturation by histone H2A deubiquitinase, MYSM1
Vijayalakshmi Nandakumar, YuChia Chou, Linda Zang, Xue F. Huang, and Si-Yi Chen
Natural killer (NK) cells are lymphocytes that kill virus-infected and tumor cells as well as activate adaptive immunity through cytokine production. Although several transcription factors have been identified as having roles in NK cell development, little is known about the transcriptional control of these transcription factors and the epigenetic control of NK cell development. In this study (pp. E3927–E3936) we identified the importance of MYSM1, a histone H2A deubiquitinase, for NK cell maturation. We found that MYSM1-mediated epigenetic alterations control the expression of an important NK cell transcription factor, inhibitor of DNA-binding protein (ID2). This study unfolds the regulatory events of key transcription factors of NK cell development such as nuclear factor IL-3 and ID2 through an epigenetic mechanism.
14-3-3σ stabilizes a complex of soluble actin and intermediate filament to enable breast tumor invasion
Aaron Boudreau, Kandice Tanner, Daojing Wang, Felipe C. Geyer, Jorge S. Reis-Filho, and Mina J. Bissell
We characterize a mechanism by which 14-3-3σ directs cell migration and tumor invasion through regulating cytoskeletal solubility and dynamics. Our data suggest (pp. E3937–E3944) that 14-3-3σ expression, rather than being a tumor suppressor, in fact, aids in breast tumor invasion at least in a subset of carcinomas. Our findings warrant further investigation into the role of this molecule in normal mammary gland and breast tumors and, indeed, in epithelial tissues and tumors where 14-3-3σ is expressed.
Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo
Abid Oueslati, Bernard L. Schneider, Patrick Aebischer, and Hilal A. Lashuel
Converging lines of evidence suggest that increase in α-syn levels plays a central role in synucleinopathies pathogenesis. Therefore, lowering α-syn levels represents a viable therapeutic strategy for these disorders. Here (pp. E3945–E3954), we describe a previously uncharacterized cellular mechanism controlling the selective autophagic degradation of α-syn. This effect is governed by PLK2 kinase activity, phosphorylation of α-syn, and PLK2/α-syn complex formation. In a rat model of Parkinson disease, PLK2 overexpression reduces α-syn levels and suppresses α-syn–induced toxicity and motor deficits. Collectively, our data support the neuroprotective role of PLK2 and suggest that modulating its activity is a viable therapeutic strategy for the treatment of Parkinson disease and related synucleinopathies.
Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes
Hannah E. Boycott, Camille S. M. Barbier, Catherine A. Eichel, Kevin D. Costa, Raphael P. Martins, Florent Louault, Gilles Dilanian, Alain Coulombe, Stéphane N. Hatem, and Elise Balse
The heart is continuously subjected to mechanical forces. The atria in particular are susceptible to changes in the mechanical environment due to their unique position as “pressure sensors.” Here (pp. E3955–E3964), we show that increased shear stress induces the recruitment of potassium channels from intracellular storage pools to the plasma membrane, via signaling pathways that link the extracellular matrix to the cytoskeleton. This process is altered in myocytes experiencing chronically increased mechanical stress. The incorporation of channels into the membrane causes changes in the electrical activity of the myocyte and may be an important way for cells to adapt to increased mechanical forces.
Preverbal infants expect members of social groups to act alike
Lindsey J. Powell and Elizabeth S. Spelke
Adults and children conform to members of their social groups and expect others to do the same, but the earlier development of this expectation is unknown. Through looking-time experiments with 7- to 12-month-old infants, we show (pp. E3965–E3972) that preverbal infants expect members of social groups to act alike. Our findings further reveal that this expectation is specific to social groups, as infants did not expect similar actions from socially unrelated individuals or from groups of inanimate objects. Thus, an expectation that social affiliates will share behaviors arises early in human development, prior to language or to extensive experience with different social groups.