Thyroid hormone-regulated chromatin landscape and transcriptional sensitivity of the pituitary gland.

Thyroid hormone (3,5,3'-triiodothyronine, T3) is a key regulator of pituitary gland function. The response to T3 is thought to hinge crucially on interactions of nuclear T3 receptors with enhancers but these sites in pituitary chromatin remain surprisingly obscure. Here, we investigate genome-wide receptor binding in mice using tagged endogenous thyroid hormone receptor ß (TRß) and analyze T3-regulated open chromatin using an anterior pituitary-specific Cre driver (Thrbb2Cre). Strikingly, T3 regulates histone modifications and chromatin opening primarily at sites that maintain TRß binding regardless of T3 levels rather than at sites where T3 abolishes or induces de novo binding. These sites associate more frequently with T3-activated than T3-suppressed genes. TRß-deficiency blunts T3-regulated gene expression, indicating that TRß confers transcriptional sensitivity. We propose a model of gene activation in which poised receptor-enhancer complexes facilitate adjustable responses to T3 fluctuations, suggesting a genomic basis for T3-dependent pituitary function or pituitary dysfunction in thyroid disorders.

Transcriptional control of cone photoreceptor diversity by a thyroid hormone receptor.

Cone photoreceptor diversity allows detection of wavelength information in light, the first step in color (chromatic) vision. In most mammals, cones express opsin photopigments for sensitivity to medium/long (M, "green") or short (S, "blue") wavelengths and are differentially arrayed over the retina. Cones appear early in retinal neurogenesis but little is understood of the subsequent control of diversity of these postmitotic neurons, because cone populations are sparse and, apart from opsins, poorly defined. It is also a challenge to distinguish potentially subtle differences between cell subtypes within a lineage. Therefore, we derived a Cre driver to isolate individual M and S opsin-enriched cones, which are distributed in counter-gradients over the mouse retina. Fine resolution transcriptome analyses identified expression gradients for groups of genes. The postnatal emergence of gradients indicated divergent differentiation of cone precursors during maturation. Using genetic tagging, we demonstrated a role for thyroid hormone receptor ß2 (TRß2) in control of gradient genes, many of which are enriched for TRß2 binding sites and TRß2-regulated open chromatin. Deletion of TRß2 resulted in poorly distinguished cones regardless of retinal location. We suggest that TRß2 controls a bipotential transcriptional state to promote cone diversity and the chromatic potential of the species.

Entangling three identical particles via spatial overlap.

Quantum correlations between identical particles are at the heart of quantum technologies. Several studies with two identical particles have shown that the spatial overlap and indistinguishability between the particles are necessary for generating bipartite entanglement. On the other hand, researches on the extension to more than two-particle systems are limited by the practical difficulty to control multiple identical particles in laboratories. In this work, we propose schemes to generate two fundamental classes of genuine tripartite entanglement, i.e., GHZ and W classes, which are experimentally demonstrated using linear optics with three identical photons. We also show that the tripartite entanglement class decays from the genuine entanglement to the full separability as the particles become more distinguishable from each other. Our results support the prediction that particle indistinguishability is a fundamental element for entangling identical particles.

Demonstration of Complete Information Trade-Off in Quantum Measurement.

While an information-disturbance trade-off in quantum measurement has been at the core of foundational quantum physics and constitutes a basis of secure quantum information processing, recently verified reversibility of a quantum measurement requires to refine it toward a complete version of information trade-off in quantum measurement. Here we experimentally demonstrate a trade-off relation among all information contents, i.e., information gain, disturbance, and reversibility in quantum measurement. By exploring quantum measurements applied on a photonic qutrit, we observe that the information of a quantum state is split into three distinct parts accounting for the extracted, disturbed, and reversible information. We verify that such different parts of information are in trade-off relations not only pairwise but also triplewise all at once, and find that the triplewise relation is tighter than any of the pairwise relations. Finally, we realize optimal quantum measurements that inherently preserve quantum information without loss of information, which offer wider applications in measurement-based quantum information processing.

Sub-10 nm Precision Engineering of Solid-State Defects via Nanoscale Aperture Array Mask.

Engineering a strongly interacting uniform qubit cluster would be a major step toward realizing a scalable quantum system for quantum sensing and a node-based qubit register. For a solid-state system that uses a defect as a qubit, various methods to precisely position defects have been developed, yet the large-scale fabrication of qubits within the strong coupling regime at room temperature continues to be a challenge. In this work, we generate nitrogen vacancy (NV) color centers in diamond with sub-10 nm scale precision using a combination of nanoscale aperture arrays (NAAs) with a high aspect ratio of 10 and a secondary E-beam hole pattern used as an ion-blocking mask. We perform optical and spin measurements on a cluster of NV spins and statistically investigate the effect of the NAAs during an ion-implantation process. We discuss how this technique is effective for constructing a scalable system.

Comparison of precutting endoscopic mucosal resection and endoscopic submucosal dissection for large (20-30 mm) flat colorectal lesions.

BACKGROUND AND AIM: The complete and safe removal of large (≥ 20 mm) colorectal lesions is an area of concern. Endoscopic submucosal dissection (ESD) effectively removes these lesions compared with endoscopic mucosal resection (EMR). However, ESD requires advanced techniques, longer procedure time, and high cost. Precutting EMR (EMR-P) is a modified EMR method that overcomes the limitations of EMR. This study aimed to compare the efficacy and safety of EMR-P and ESD in large (20-30 mm) flat colorectal lesions. METHODS: This was a retrospective analysis of cases in which 20- to 30-mm flat colorectal lesions were resected at Seoul St. Mary's Hospital from January 2014 to December 2019. Propensity score matching was performed to control for possible confounders. RESULTS: Two hundred and ninety-nine patients were included in this study. After matching, 90 patients were assigned to each group. There were no significant difference in complete resection rates (92.2% vs 92.2%, P = 1.000), en bloc resection rates (95.6% vs 97.8%, P = 0.682), and mean size of lesions (22.9 ± 3.1 mm vs 23.0 ± 3.1 mm, P = 0.867) between EMR-P and ESD. Procedure time was significantly shorter with EMR-P (11.0 ± 6.5 min vs 37.0 ± 19.3 min, P < 0.001). The adverse events rate was not significantly different between both groups. No local recurrence occurred in both groups. CONCLUSIONS: Precutting EMR was not significantly different to ESD in terms of complete resection rate and en bloc resection rate for 20- to 30-mm flat colorectal lesions without fibrosis. Furthermore, EMR-P has shorter procedure time than ESD. EMR-P could be considered one of standard treatments for large flat colorectal lesions.

Screening Leads to Overestimated Associations of Thyroid Dysfunction and Thyroiditis with Thyroid Cancer Risk.

We aimed to assess the relationships of functional thyroid disease and thyroiditis with subsequent thyroid cancer, which is controversial due to various confounders, and the effect of thyroid disease workup on this association. We used the cohort data from 2002 to 2015 (Study I, n = 28,330) and the entire data from 2002 to 2019 (Study II, n = 883,074) of the Korean National Health Insurance Service database, and performed logistic regression and subgroup analyses with various covariates. In Study I, hypothyroidism, thyroiditis, autoimmune thyroiditis, hyperthyroidism, and Graves' disease showed positive associations with thyroid cancer. In Study II, after adjustment for covariates including the number of thyroid function tests, the ORs for thyroid cancer were significantly reduced in all thyroid diseases. Hypothyroidism, thyroiditis, and autoimmune thyroiditis were positively associated (adjusted odds ratio, OR (95% confidence interval, CI) 1.28 (1.25-1.32), 1.36 (1.31-1.42), and 1.17 (1.11-1.24), respectively), whereas hyperthyroidism and Graves' disease were negatively associated with thyroid cancer (adjusted OR (95% CI) 0.80 (0.77-0.83) and 0.69 (0.65-0.74), respectively). Multiple subgroup analyses in both studies showed consistent results. In this large population-based, nationwide study, we confirmed that thyroid disease workup leads to overestimation of associations of thyroid dysfunction and thyroiditis with thyroid cancer risk.

Implementation of a 3 × 3 directionally-unbiased linear optical multiport.

Linear optical multiports are widely used in photonic quantum information processing. Naturally, these devices are directionally-biased since photons always propagate from the input ports toward the output ports. Recently, the concept of directionally-unbiased linear optical multiports was proposed. These directionally-unbiased multiports allow photons to propagate along a reverse direction, which can greatly reduce the number of required linear optical elements for complicated linear optical quantum networks. Here, we report an experimental demonstration of a 3 × 3 directionally-unbiased linear optical fiber multiport using an optical tritter and mirrors. Compared to the previous demonstration using bulk optical elements which works only with light sources with a long coherence length, our experimental directionally-unbiased 3 × 3 optical multiport does not require a long coherence length since it provides negligible optical path length differences among all possible optical trajectories. It can be a useful building block for implementing large-scale quantum walks on complex graph networks.

Quantum enhanced multiple-phase estimation with multi-mode N00N states.

Quantum metrology can achieve enhanced sensitivity for estimating unknown parameters beyond the standard quantum limit. Recently, multiple-phase estimation exploiting quantum resources has attracted intensive interest for its applications in quantum imaging and sensor networks. For multiple-phase estimation, the amount of enhanced sensitivity is dependent on quantum probe states, and multi-mode N00N states are known to be a key resource for this. However, its experimental demonstration has been missing so far since generating such states is highly challenging. Here, we report generation of multi-mode N00N states and experimental demonstration of quantum enhanced multiple-phase estimation using the multi-mode N00N states. In particular, we show that the quantum Cramer-Rao bound can be saturated using our two-photon four-mode N00N state and measurement scheme using a 4 × 4 multi-mode beam splitter. Our multiple-phase estimation strategy provides a faithful platform to investigate multiple parameter estimation scenarios.

A coregulator shift, rather than the canonical switch, underlies thyroid hormone action in the liver.

Thyroid hormones (THs) are powerful regulators of metabolism with major effects on body weight, cholesterol, and liver fat that have been exploited pharmacologically for many years. Activation of gene expression by TH action is canonically ascribed to a hormone-dependent "switch" from corepressor to activator binding to thyroid hormone receptors (TRs), while the mechanism of TH-dependent repression is controversial. To address this, we generated a mouse line in which endogenous TRß1 was epitope-tagged to allow precise chromatin immunoprecipitation at the low physiological levels of TR and defined high-confidence binding sites where TRs functioned at enhancers regulated in the same direction as the nearest gene in a TRß-dependent manner. Remarkably, although positive and negative regulation by THs have been ascribed to different mechanisms, TR binding was highly enriched at canonical DR4 motifs irrespective of the transcriptional direction of the enhancer. The canonical NCoR1/HDAC3 corepressor complex was reduced but not completely dismissed by TH and, surprisingly, similar effects were seen at enhancers associated with negatively as well as positively regulated genes. Conversely, coactivator CBP was found at all TH-regulated enhancers, with transcriptional activity correlating with the ratio of CBP to NCoR rather than their presence or absence. These results demonstrate that, in contrast to the canonical "all or none" coregulator switch model, THs regulate gene expression by orchestrating a shift in the relative binding of corepressors and coactivators.

Diamond photonic crystal mirror with a partial bandgap by two 2D photonic crystal layers.

In this study, photonic crystals with a partial bandgap are demonstrated in the visible region using single-crystal diamonds. Quasi-three-dimensional photonic crystal structures are fabricated in the surface of the single-crystal diamonds using a tetrahedron Faraday cage that enables angled dry etching in three directions simultaneously. The reflection spectra can be controlled by varying the lattice constant of the photonic crystals. In addition, nitrogen-vacancy center single-photon sources are implanted on top of the diamond photonic crystals, and doubled collection efficiency from the light sources is achieved.

Entangling bosons through particle indistinguishability and spatial overlap.

Particle identity and entanglement are two fundamental quantum properties that work as major resources for various quantum information tasks. However, it is still a challenging problem to understand the correlation of the two properties in the same system. While recent theoretical studies have shown that the spatial overlap between identical particles is necessary for nontrivial entanglement, the exact role of particle indistinguishability in the entanglement of identical particles has never been analyzed quantitatively before. Here, we theoretically and experimentally investigate the behavior of entanglement between two bosons as spatial overlap and indistinguishability simultaneously vary. The theoretical computation of entanglement for generic two bosons with pseudospins is verified experimentally in a photonic system. Our results show that the amount of entanglement is a monotonically increasing function of both quantities. We expect that our work provides an insight into deciphering the role of the entanglement in quantum networks that consist of identical particles.

MLL3/MLL4-Associated PAGR1 Regulates Adipogenesis by Controlling Induction of C/EBPß and C/EBPδ.

Transcription factors C/EBPß and C/EBPδ are induced within hours after initiation of adipogenesis in culture. They directly promote the expression of master adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα and are required for adipogenesis in vivo However, the mechanism that controls the induction of C/EBPß and C/EBPδ remains elusive. We previously showed that histone methyltransferases MLL3/MLL4 and associated PTIP are required for the induction of PPARγ and C/EBPα during adipogenesis. Here, we show MLL3/MLL4/PTIP-associated protein PAGR1 (also known as PA1) cooperates with phosphorylated CREB and ligand-activated glucocorticoid receptor to directly control the induction of C/EBPß and C/EBPδ in the early phase of adipogenesis. Deletion of Pagr1 in white and brown preadipocytes prevents the induction of C/EBPß and C/EBPδ and leads to severe defects in adipogenesis. Adipogenesis defects in PAGR1-deficient cells can be rescued by the ectopic expression of C/EBPß or PPARγ. Finally, the deletion of Pagr1 in Myf5+ precursor cells impairs brown adipose tissue and muscle development. Thus, by controlling the induction of C/EBPß and C/EBPδ, PAGR1 plays a critical role in adipogenesis.

Emilin 2 promotes the mechanical gradient of the cochlear basilar membrane and resolution of frequencies in sound.

The detection of different frequencies in sound is accomplished with remarkable precision by the basilar membrane (BM), an elastic, ribbon-like structure with graded stiffness along the cochlear spiral. Sound stimulates a wave of displacement along the BM with maximal magnitude at precise, frequency-specific locations to excite neural signals that carry frequency information to the brain. Perceptual frequency discrimination requires fine resolution of this frequency map, but little is known of the intrinsic molecular features that demarcate the place of response on the BM. To investigate the role of BM microarchitecture in frequency discrimination, we deleted extracellular matrix protein emilin 2, which disturbed the filamentous organization in the BM. Emilin2 -/- mice displayed broadened mechanical and neural frequency tuning with multiple response peaks that are shifted to lower frequencies than normal. Thus, emilin 2 confers a stiffness gradient on the BM that is critical for accurate frequency resolution.

Universal Compressive Characterization of Quantum Dynamics.

Recent quantum technologies utilize complex multidimensional processes that govern the dynamics of quantum systems. We develop an adaptive diagonal-element-probing compression technique that feasibly characterizes any unknown quantum processes using much fewer measurements compared to conventional methods. This technique utilizes compressive projective measurements that are generalizable to an arbitrary number of subsystems. Both numerical analysis and experimental results with unitary gates demonstrate low measurement costs, of order O(d^{2}) for d-dimensional systems, and robustness against statistical noise. Our work potentially paves the way for a reliable and highly compressive characterization of general quantum devices.

Reference-frame-independent, measurement-device-independent quantum key distribution using fewer quantum states.

Reference-frame-independent quantum key distribution (RFI-QKD) provides a practical way to generate secret keys between two remote parties without sharing common reference frames. On the other hand, measurement-device-independent QKD (MDI-QKD) offers a high level of security, as it is immune to all quantum hacking attempts to measurement devices. The combination of these two QKD protocols, i.e., RFI-MDI-QKD, is one of the most fascinating QKD protocols, since it holds advantages of both practicality and security. For further practicality of RFI-MDI-QKD, it is beneficial to reduce the implementation complexity. Here, we show that RFI-MDI-QKD can be implemented using fewer quantum states than those of its original proposal. We find that, in principle, the number of quantum states for one of the parties can be reduced from six to three without compromising security. Compared to conventional RFI-MDI-QKD where both parties transmit six quantum states, it significantly simplifies the implementation of the QKD protocol. We also verify the feasibility of the scheme with a proof-of-principle experiment.

H2B ubiquitylation enhances H3K4 methylation activities of human KMT2 family complexes.

In mammalian cells, distinct H3K4 methylation states are created by deposition of methyl groups by multiple complexes of histone lysine methyltransferase 2 (KMT2) family proteins. For comprehensive analyses that directly compare the catalytic properties of all six human KMT2 complexes, we employed a biochemically defined system reconstituted with recombinant KMT2 core complexes (KMT2CoreCs) containing minimal components required for nucleosomal H3K4 methylation activity. We found that each KMT2CoreC generates distinct states and different levels of H3K4 methylation, and except for MLL3 all are stimulated by H2Bub. Notably, SET1BCoreC exhibited the strongest H3K4 methylation activity and, to our surprise, did not require H2B ubiquitylation (H2Bub); in contrast, H2Bub was required for the H3K4me2/3 activity of the paralog SET1ACoreC. We also found that WDR5, RbBP5, ASH2L and DPY30 are required for efficient H3K4 methyltransferase activities of all KMT2CoreCs except MLL3, which could produce H3K4me1 in the absence of WDR5. Importantly, deletion of the PHD2 domain of CFP1 led to complete loss of the H3K4me2/3 activities of SET1A/BCoreCs in the presence of H2Bub, indicating a critical role for this domain in the H2Bub-stimulated H3K4 methylation. Collectively, our results suggest that each KMT2 complex methylates H3K4 through distinct mechanisms in which individual subunits differentially participate.

Informationally symmetrical Bell state preparation and measurement.

Bell state measurement (BSM) plays crucial roles in photonic quantum information processing. The standard linear optical BSM is based on Hong-Ou-Mandel interference where two photons meet and interfere at a beamsplitter (BS). However, a generalized two-photon interference is not based on photon-photon interaction, but interference between two-photon probability amplitudes. Therefore, it might be possible to implement BSM without interfering photons at a BS. Here, we investigate a linear optical BSM scheme which does not require two photon overlapping at a BS. By unleashing the two photon coexistence condition, it can be symmetrically divided into two parties. The symmetrically dividable property suggests an informationally symmetrical BSM between remote parties without a third party. We also present that our BSM scheme can be used for Bell state preparation between remote parties without a third party. Since our BSM scheme can be easily extended to multiple photons, it can be useful for various quantum communication applications.