RIM and RIM-BP Form Presynaptic Active-Zone-like Condensates via Phase Separation.

Both the timing and kinetics of neurotransmitter release depend on the positioning of clustered Ca2+ channels in active zones to docked synaptic vesicles on presynaptic plasma membranes. However, how active zones form is not known. Here, we show that RIM and RIM-BP, via specific multivalent bindings, form dynamic and condensed assemblies through liquid-liquid phase separation. Voltage-gated Ca2+ channels (VGCCs), via C-terminal-tail-mediated direct binding to both RIM and RIM-BP, can be enriched to the RIM and RIM-BP condensates. We further show that RIM and RIM-BP, together with VGCCs, form dense clusters on the supported lipid membrane bilayers via phase separation. Therefore, RIMs and RIM-BPs are plausible organizers of active zones, and the formation of RIM and RIM-BP condensates may cluster VGCCs into nano- or microdomains and position the clustered Ca2+ channels with Ca2+ sensors on docked vesicles for efficient and precise synaptic transmissions.

Quantum Squeezing and Sensing with Pseudo-Anti-Parity-Time Symmetry.

The emergence of parity-time (PT) symmetry has greatly enriched our study of symmetry-enabled non-Hermitian physics, but the realization of quantum PT symmetry faces an intrinsic issue of unavoidable symmetry-breaking Langevin noises. Here we construct a quantum pseudo-anti-PT (pseudo-APT) symmetry in a two-mode bosonic system without involving Langevin noises. We show that the spontaneous pseudo-APT symmetry breaking leads to an exceptional point, across which there is a transition between different types of quantum squeezing dynamics; i.e., the squeezing factor increases exponentially (oscillates periodically) with time in the pseudo-APT-symmetric (broken) region. Such dramatic changes of squeezing factors and quantum dynamics near the exceptional point are utilized for ultraprecision quantum sensing. These exotic quantum phenomena and sensing applications can be experimentally observed in two physical systems: spontaneous wave mixing nonlinear optics and atomic Bose-Einstein condensates. Our Letter offers a physical platform for investigating exciting APT symmetry physics in the quantum realm, paving the way for exploring fundamental quantum non-Hermitian effects and their quantum technological applications.

Tailor-made unitary operations using dielectric metasurfaces.

Qubit operation belonging to unitary transformation is the fundamental operation to realize quantum computing and information processing. Here, we show that the complex and flexible light-matter interaction between dielectric metasurfaces and incident light can be used to perform arbitrary U(2) operations. By incorporating both coherent spatial-mode operation together with two polarizations on a single metasurface, we further extend the discussion to single-photon two-qubit U(4) operations. We believe the efficient usage of metasurfaces as a potential compact platform can simplify optical qubit operation from bulky systems into conceptually subwavelength elements.

ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.

ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. In keeping with this, both proteins bind to AP-2 complex components as well as to clathrin, suggesting roles in endocytosis and vesicle recycling. The two proteins play complementary roles in the DDR; ATM is engaged in the repair of double-strand breaks, while ATR deals mainly with single-strand damage. Unexpectedly, this complementarity extends to these proteins' synaptic function as well. Superresolution microscopy and coimmunoprecipitation reveal that ATM associates exclusively with excitatory (VGLUT1+) vesicles, while ATR associates only with inhibitory (VGAT+) vesicles. The levels of ATM and ATR respond to each other; when ATM is deficient, ATR levels rise, and vice versa. Finally, blocking NMDA, but not GABA, receptors causes ATM levels to rise while ATR levels respond to GABA, but not NMDA, receptor blockade. Taken together, our data suggest that ATM and ATR are part of the cellular "infrastructure" that maintains the excitatory/inhibitory balance of the nervous system. This idea has important implications for the human diseases resulting from their genetic deficiency.

Einstein-Podolsky-Rosen Energy-Time Entanglement of Narrow-Band Biphotons.

We report the direct characterization of energy-time entanglement of narrow-band biphotons produced from spontaneous four-wave mixing in cold atoms. The Stokes and anti-Stokes two-photon temporal correlation is measured by single-photon counters with nanosecond temporal resolution, and their joint spectrum is determined by using a narrow linewidth optical cavity. The energy-time entanglement is verified by the joint frequency-time uncertainty product of 0.063±0.0044, which does not only violate the separability criterion but also satisfies the continuous variable Einstein-Podolsky-Rosen steering inequality.

Cdk5-dependent phosphorylation of liprinα1 mediates neuronal activity-dependent synapse development.

The experience-dependent modulation of brain circuitry depends on dynamic changes in synaptic connections that are guided by neuronal activity. In particular, postsynaptic maturation requires changes in dendritic spine morphology, the targeting of postsynaptic proteins, and the insertion of synaptic neurotransmitter receptors. Thus, it is critical to understand how neuronal activity controls postsynaptic maturation. Here we report that the scaffold protein liprinα1 and its phosphorylation by cyclin-dependent kinase 5 (Cdk5) are critical for the maturation of excitatory synapses through regulation of the synaptic localization of the major postsynaptic organizer postsynaptic density (PSD)-95. Whereas Cdk5 phosphorylates liprinα1 at Thr701, this phosphorylation decreases in neurons in response to neuronal activity. Blockade of liprinα1 phosphorylation enhances the structural and functional maturation of excitatory synapses. Nanoscale superresolution imaging reveals that inhibition of liprinα1 phosphorylation increases the colocalization of liprinα1 with PSD-95. Furthermore, disruption of liprinα1 phosphorylation by a small interfering peptide, siLIP, promotes the synaptic localization of PSD-95 and enhances synaptic strength in vivo. Our findings collectively demonstrate that the Cdk5-dependent phosphorylation of liprinα1 is important for the postsynaptic organization during activity-dependent synapse development.

Anti-Parity-Time Symmetric Optical Four-Wave Mixing in Cold Atoms.

Non-Hermitian optical systems with parity-time (PT) symmetry have recently revealed many intriguing prospects that outperform conservative structures. The previous works are mostly rooted in complex arrangements with controlled gain-loss interplay. Here, we demonstrate anti-PT symmetry inherent in the nonlinear optical interaction based upon forward optical four-wave mixing in a laser-cooled atomic ensemble with negligible linear gain and loss. We observe that the pair of frequency modes undergo a nontrivial anti-PT phase transition between coherent power oscillation and optical parametric amplification in presence of a large phase mismatch.

δ-Quench Measurement of a Pure Quantum-State Wave Function.

The measurement of a quantum state wave function not only acts as a fundamental part in quantum physics but also plays an important role in developing practical quantum technologies. Conventional quantum state tomography has been widely used to estimate quantum wave functions, which usually requires complicated measurement techniques. The recent weak-value-based quantum measurement circumvents this resource issue but relies on an extra pointer space. Here, we theoretically propose and then experimentally demonstrate a direct and efficient measurement strategy based on a δ-quench probe: by quenching its complex probability amplitude one by one (δ quench) in the given basis, we can directly obtain the quantum wave function of a pure ensemble by projecting the quenched state onto a postselection state. We confirm its power by experimentally measuring photonic complex temporal wave functions. This new method is versatile and can find applications in quantum information science and engineering.

TEFM Enhances Transcription Elongation by Modifying mtRNAP Pausing Dynamics.

Regulation of transcription elongation is one of the key mechanisms employed to control gene expression. The single-subunit mitochondrial RNA polymerase (mtRNAP) transcribes mitochondrial genes, such as those related to ATP synthesis. We investigated how mitochondrial transcription elongation factor (TEFM) enhances mtRNAP transcription elongation using a single-molecule optical-tweezers transcription assay, which follows transcription dynamics in real time and allows the separation of pause-free elongation from transcriptional pauses. We found that TEFM enhances the stall force of mtRNAP. Although TEFM does not change the pause-free elongation rate, it enhances mtRNAP transcription elongation by reducing the frequency of long-lived pauses and shortening their durations. Furthermore, we demonstrate how mtRNAP passes through the conserved sequence block II, which is the key sequence for the switch between DNA replication and transcription in mitochondria. Our findings elucidate how both TEFM and mitochondrial genomic DNA sequences directly control the transcription elongation dynamics of mtRNAP.

Development of in Planta Chemical Cross-Linking-Based Quantitative Interactomics in Arabidopsis.

An in planta chemical cross-linking-based quantitative interactomics (IPQCX-MS) workflow has been developed to investigate in vivo protein-protein interactions and alteration in protein structures in a model organism, Arabidopsis thaliana. A chemical cross-linker, azide-tag-modified disuccinimidyl pimelate (AMDSP), was directly applied onto Arabidopsis tissues. Peptides produced from protein fractions of CsCl density gradient centrifugation were dimethyl-labeled, from which the AMDSP cross-linked peptides were fractionated on chromatography, enriched, and analyzed by mass spectrometry. ECL2 and SQUA-D software were used to identify and quantitate these cross-linked peptides, respectively. These computer programs integrate peptide identification with quantitation and statistical evaluation. This workflow eventually identified 354 unique cross-linked peptides, including 61 and 293 inter- and intraprotein cross-linked peptides, respectively, demonstrating that it is able to in vivo identify hundreds of cross-linked peptides at an organismal level by overcoming the difficulties caused by multiple cellular structures and complex secondary metabolites of plants. Coimmunoprecipitation and super-resolution microscopy studies have confirmed the PHB3-PHB6 protein interaction found by IPQCX-MS. The quantitative interactomics also found hormone-induced structural changes of SBPase and other proteins. This mass-spectrometry-based interactomics will be useful in the study of in vivo protein-protein interaction networks in agricultural crops and plant-microbe interactions.

A Distinct Pathway for Polar Exocytosis in Plant Cell Wall Formation.

Post-Golgi protein sorting and trafficking to the plasma membrane (PM) is generally believed to occur via the trans-Golgi network (TGN). In this study using Nicotiana tabacum pectin methylesterase (NtPPME1) as a marker, we have identified a TGN-independent polar exocytosis pathway that mediates cell wall formation during cell expansion and cytokinesis. Confocal immunofluorescence and immunogold electron microscopy studies demonstrated that Golgi-derived secretory vesicles (GDSVs) labeled by NtPPME1-GFP are distinct from those organelles belonging to the conventional post-Golgi exocytosis pathway. In addition, pharmaceutical treatments, superresolution imaging, and dynamic studies suggest that NtPPME1 follows a polar exocytic process from Golgi-GDSV-PM/cell plate (CP), which is distinct from the conventional Golgi-TGN-PM/CP secretion pathway. Further studies show that ROP1 regulates this specific polar exocytic pathway. Taken together, we have demonstrated an alternative TGN-independent Golgi-to-PM polar exocytic route, which mediates secretion of NtPPME1 for cell wall formation during cell expansion and cytokinesis and is ROP1-dependent.

Quantum Heat Engine Using Electromagnetically Induced Transparency.

We report an experiment demonstrating the generation of directional thermal radiation with a spectral brightness that is about 9 times greater than that of the ambient pumping reservoir. The experiment is based on the recent proposal for a nontraditional quantum heat engine and uses cold Rb atoms, electromagnetically induced transparency, and photon correlation spectroscopy [Phys. Rev. A 94, 053859 (2016)PLRAAN2469-992610.1103/PhysRevA.94.053859].

Mirrorless Optical Parametric Oscillation with Tunable Threshold in Cold Atoms.

We report the demonstration of a mirrorless optical parametric oscillator with a tunable threshold in laser-cooled atoms with four-wave mixing (FWM) using electromagnetically induced transparency. Driven by two classical laser beams, the generated Stokes and anti-Stokes fields counterpropagate and build up efficient intrinsic feedback through the nonlinear FWM process. This feedback does not involve any cavity or spatially distributed microstructures. We observe the transition of photon correlation properties from the biphoton quantum regime (below the threshold) to the oscillation regime (above the threshold). The pump threshold can be tuned by varying the operating parameters. We achieve the oscillation with a threshold as low as 15 µW.

ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity.

Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology.

A user-friendly two-color super-resolution localization microscope.

We report a robust two-color method for super-resolution localization microscopy. Two-dye combination of Alexa647 and Alexa750 in an imaging buffer containing COT and using TCEP as switching regent provides matched and balanced switching characteristics for both dyes, allowing simultaneous capture of both on a single camera. Active sample locking stabilizes sample with 1nm accuracy during imaging. With over 4,000 photons emitted from both dyes, two-color superresolution images with high-quality were obtained in a wide range of samples including cell cultures, tissue sections and yeast cells.

Measuring the biphoton temporal wave function with polarization-dependent and time-resolved two-photon interference.

We propose and demonstrate an approach to measuring the biphoton temporal wave function with polarization-dependent and time-resolved two-photon interference. Through six sets of two-photon interference measurements projected onto different polarization subspaces, we can reconstruct the amplitude and phase functions of the biphoton temporal waveform. For the first time, we apply this technique to experimentally determine the temporal quantum states of the narrow-band biphotons generated from the spontaneous four-wave mixing in cold atoms.

Shaping the Biphoton Temporal Waveform with Spatial Light Modulation.

We demonstrate a technique for shaping the temporal wave function of biphotons generated from spatially modulated spontaneous four-wave mixing in cold atoms. We show that the spatial profile of the pump field can be mapped onto the biphoton temporal wave function in the group delay regime. The spatial profile of the pump laser beam is shaped by using a spatial light modulator. This spatial-to-temporal mapping enables the generation of narrow-band biphotons with controllable temporal waveforms.

Manipulating photon emission efficiency with local electronic states in a tunneling gap.

We demonstrate manipulation of photon emission efficiency in a tunneling gap by tuning the rates of elastic and inelastic electron tunneling processes with local electronic states. The artificial local electronic states are created by a scanning tunneling microscope tip on a CuN nanoisland grown on a Cu(100) surface at cryogenic temperature. These local electronic states can either enhance or suppress the excitation of tip-induced surface plasmon modes at specific bias voltages, and thus the induced photon emission rates. A theoretical model quantitatively analyzing inelastic and elastic tunneling processes associated with characteristic electronic states shows good agreement with experiments. We also show that tip-induced photon emission measurement can be used for probing the electronic states in the tunneling gap.

Efficiently loading a single photon into a single-sided Fabry-Perot cavity.

We demonstrate that a single photon with an optimal temporal waveform can be efficiently loaded into a cavity. Using heralded narrow-band single photons with exponential growth wave packet shaped by an electro-optical amplitude modulator, whose time constant matches the photon lifetime in the cavity, we demonstrate a loading efficiency of (87±2)% from free space to a single-sided Fabry-Perot cavity. We further demonstrate directly loading heralded single Stokes photons into the cavity with an efficiency of (60±5)% without the electro-optical amplitude modulator and verify the time reversal between the frequency-entangled paired photons. Our result and approach may enable promising applications in realizing large-scale quantum networks based on cavity quantum electrodynamics.

Subnatural-linewidth polarization-entangled photon pairs with controllable temporal length.

We demonstrate an efficient experimental scheme for producing polarization-entangled photon pairs from spontaneous four-wave mixing (SFWM) in a laser-cooled (85)Rb atomic ensemble, with a bandwidth (as low as 0.8 MHz) much narrower than the rubidium atomic natural linewidth. By stabilizing the relative phase between the two SFWM paths in a Mach-Zehnder interferometer configuration, we are able to produce all four Bell states. These subnatural-linewidth photon pairs with polarization entanglement are ideal quantum information carriers for connecting remote atomic quantum nodes via efficient light-matter interaction in a photon-atom quantum network.