Endosomes serve as signaling platforms for RIG-I ubiquitination and activation.

RIG-I-like receptors (RLRs) are cytosolic RNA sensors critical for antiviral immunity. RLR activation is regulated by polyubiquitination and oligomerization following RNA binding. Yet, little is known about how RLRs exploit subcellular organelles to facilitate their posttranslational modifications and activation.

High-frequency neural activity dysregulation is associated with sleep and psychiatric disorders in BMAL1-deficient animal models.

Sleep disturbance led by BMAL1-deficiency has been recognized both in rodent and non-human primate models. Yet it remained unclear how their diurnal brain oscillations were affected upon BMAL1 ablation and what caused the discrepancy in the quantity of sleep between the two species. Here, we investigated diurnal electroencephalographs of BMAL1-deficient mice and cynomolgus monkeys at young adult age and uncovered a shared defect of dysregulated high-frequency oscillations by Kullback-Leibler divergence analysis.

ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude.

Circadian dysregulation associates with numerous diseases including metabolic dysfunction, sleep disorder, depression and aging. Given that declined circadian amplitude is a trait commonly found with compromised health, interventions that design in precluding circadian amplitude from dampening will aid to mitigate complex, circadian-related diseases. Here we identify a neurogenic small molecule ISX-9 that is able to support persistent and higher amplitude of circadian oscillations.

Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy.

Presynaptic syntaxin binding protein 1 (STXBP1) is essential for neurotransmitter release. Heterozygous mutations in this protein cause STXBP1 encephalopathy (STXBP1-E), which is characterized by intellectual disabilities and epilepsies. Since nonhuman primates closely resemble humans, monkey models may advance studies on the pathogenesis and therapeutic treatments of STXBP1-E.

Influenza a virus NS1 resembles a TRAF3-interacting motif to target the RNA sensing-TRAF3-type I IFN axis and impair antiviral innate immunity.

Background: Influenza A virus (IAV) evolves strategies to counteract the host antiviral defense for establishing infection. The influenza A virus (IAV) non-structural protein 1 (NS1) is a key viral factor shown to counteract type I IFN antiviral response mainly through targeting RIG-I signaling. Growing evidence suggests that viral RNA sensors RIG-I, TLR3, and TLR7 function to detect IAV RNA in different cell types to induce type I IFN antiviral response to IAV infection.

SIRT7 Facilitates CENP-A Nucleosome Assembly and Suppresses Intestinal Tumorigenesis.

SIRT7 is a member of the mammalian sirtuins and functions as an NAD-dependent deacylase. Here we show that SIRT7 deficiency leads to a lowered histone acetyltransferase 1 (HAT1) activity and therefore decreased histone H4K5 and H4K12 acetylation. This in turn causes CENP-A dislocation at the centromere, which further affects chromatin assembly.

CDK9 modulates circadian clock by attenuating REV-ERBα activity.

Circadian clock and cell cycle are vital cellular programs acting in a timely-regulated, cyclic manner. The two cellular oscillators are coupled in various ways to facilitate biological processes. Here we report CDK9, a kinase belongs to the CDK family in regulating cell cycle and RNA Pol II activity, can serve as a modulator for circadian clock.

Cloning of a gene-edited macaque monkey by somatic cell nuclear transfer.

Cloning of macaque monkeys by somatic cell nucleus transfer (SCNT) allows the generation of monkeys with uniform genetic backgrounds that are useful for the development of non-human primate models of human diseases. Here, we report the feasibility of this approach by SCNT of fibroblasts from a macaque monkey (), in which a core circadian transcription factor BMAL1 was knocked out by clustered regularly interspaced short palindromic repeat/Cas9 gene editing (see accompanying paper). Out of 325 SCNT embryos transferred into 65 surrogate monkeys, we cloned five macaque monkeys with mutations in both alleles without mosaicism, with nuclear genes identical to that of the fibroblast donor monkey.

BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders.

Circadian disruption is a risk factor for metabolic, psychiatric and age-related disorders, and non-human primate models could help to develop therapeutic treatments. Here, we report the generation of BMAL1 knockout cynomolgus monkeys for circadian-related disorders by CRISPR/Cas9 editing of monkey embryos. These monkeys showed higher nocturnal locomotion and reduced sleep, which was further exacerbated by a constant light regimen.

Neurodegeneration-associated FUS is a novel regulator of circadian gene expression.

Background: Circadian rhythms are oscillating physiological and behavioral changes governed by an internal molecular clock, and dysfunctions in circadian rhythms have been associated with ageing and various neurodegenerative diseases. However, the evidence directly connecting the neurodegeneration-associated proteins to circadian control at the molecular level remains sparse.

Methods: Using meta-analysis, synchronized animals and cell lines, cells and tissues from FUS R521C knock-in rats, we examined the role of FUS in circadian gene expression regulation.

Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin rats.

Mutations in fused in sarcoma (Fus) cause familial amyotrophic lateral sclerosis (ALS) and occasionally frontotemporal dementia. Here we report the establishment and characterization of a novel knockin (KI) rat model expressing a Fus point mutation (R521C) via CRISPR/Cas9. The mutant animals developed adult-onset learning and memory behavioral deficits, with reduced spine density in hippocampal neurons.

Leaky property of the Dyakonov-like wave at the surface of a semi-infinite metal-dielectric multilayered structure.

We investigate the Dyakonov-like surface wave (DLSW) at the interface of a dielectric and a metal-dielectric multilayered (MDM) structure when this MDM structure serves as an elliptic medium according to the effective medium approximation (EMA). Different from the conventional Dyakonov surface waves, we find that this kind of DLSW possesses an unexpected leaky property due to an additional hyperbolic-like wave in the MDM structure, resulting in a significant increase of propagation loss compared to the results estimated by a simple effective model based on the EMA. Moreover, such leaky property is found to be sensitive to the period of the MDM structure.

Determination of dissipative Dyakonov surface waves using a finite element method based eigenvalue algorithm.

A full-vectorial finite element method is developed to analyze the surface waves propagating at the interface between two media which could be dissipative particularly. The dissipative wave possessing a complex-valued propagation constant can be determined precisely for any given propagation direction and thus the property of losses could be thoroughly analyzed. Besides, by applying a special characteristic of the implicit circular block matrix, we reduce the computational consumptions in the analysis.

Physiological links of circadian clock and biological clock of aging.

Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles.

Mutation of kri1l causes definitive hematopoiesis failure via PERK-dependent excessive autophagy induction.

Dysregulation of ribosome biogenesis causes human diseases, such as Diamond-Blackfan anemia, del (5q-) syndrome and bone marrow failure. However, the mechanisms of blood disorders in these diseases remain elusive. Through genetic mapping, molecular cloning and mechanism characterization of the zebrafish mutant cas002, we reveal a novel connection between ribosomal dysfunction and excessive autophagy in the regulation of hematopoietic stem/progenitor cells (HSPCs).

Periodic anti-ring back reflectors for hydrogenated amorphous silicon thin-film solar cells.

Large and periodic anti-ring arrays are fabricated by using a monolayer of polymer/nanosphere hybrid technique and applied as back reflectors in substrate-type hydrogenated amorphous silicon (a-Si:H) thin-film solar cells. The structure of each anti-ring comprises a nanodome centered inside a nanohole. The excitation of Bloch wave surface plasmon polaritons is observed in the Ag-coated anti-ring arrays.

Enhancing bright-field image of microorganisms by local plasmon of Ag nanoparticle array.

Inspecting biological cells with bright-field light microscopy often engenders a challenge, owing to their optical transparency. We show that imaging contrast can be greatly enhanced as yeast cells are placed on a silver nanoparticle array. Its near- and far-field traits, revealed by electrodynamic simulations, illustrate that the enhancement is attributed to the sensitivity of its plasmonic characteristics to the attached cells.

SIRT1 and other sirtuins in metabolism.

Sirtuins such as SIRT1 are conserved protein NAD(+)-dependent deacylases and thus their function is intrinsically linked to cellular metabolism. Over the past two decades, accumulating evidence has indicated that sirtuins are not only important energy status sensors but also protect cells against metabolic stresses. Sirtuins regulate the aging process and are themselves regulated by diet and environmental stress.

SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging.

SIRT1 is a NAD(+)-dependent protein deacetylase that governs many physiological pathways, including circadian rhythm in peripheral tissues. Here, we show that SIRT1 in the brain governs central circadian control by activating the transcription of the two major circadian regulators, BMAL1 and CLOCK. This activation comprises an amplifying circadian loop involving SIRT1, PGC-1α, and Nampt.

DnaK functions as a central hub in the E. coli chaperone network.

Cellular chaperone networks prevent potentially toxic protein aggregation and ensure proteome integrity. Here, we used Escherichia coli as a model to understand the organization of these networks, focusing on the cooperation of the DnaK system with the upstream chaperone Trigger factor (TF) and the downstream GroEL. Quantitative proteomics revealed that DnaK interacts with at least ~700 mostly cytosolic proteins, including ~180 relatively aggregation-prone proteins that utilize DnaK extensively during and after initial folding.

Terahertz pipe-waveguide-based directional couplers.

We experimentally demonstrate a terahertz (THz) leaky mode directional coupler for future THz applications. The proposed directional coupler comprises two square pipe waveguides. The coupling efficiency is investigated for different frequencies, polarizations, and core sizes.

Terahertz polarization-sensitive rectangular pipe waveguides.

We propose square and rectangular pipe waveguides for low-loss THz waveguiding and polarization control. Different from common circular-symmetric THz fibers and waveguides, the proposed rectangular pipe waveguides successfully remove the transmission degeneracy of two orthogonal polarizations and possess polarization sensitivity to the guided THz waves. By measuring the attenuation spectra, we find that the polarization sensitivity depends on the structure of the pipe waveguides.

Terahertz antiresonant-reflecting-hollow-waveguide-based directional coupler operating at antiresonant frequencies.

We report a particular coupling phenomenon occurring in the directional coupler composed of two touching terahertz antiresonant reflecting hollow waveguides. Unlike conventional directional couplers where one even system mode and one odd system mode are excited, numerical results indicate that three (one even and two odd) system modes participate in the power transfer process at the antiresonant frequencies. As a result, the coupling length can be significantly reduced, and it is shown here to be less than 300 wavelengths.

A high-accuracy pseudospectral full-vectorial leaky optical waveguide mode solver with carefully implemented UPML absorbing boundary conditions.

The previously developed full-vectorial optical waveguide eigenmode solvers using pseudospectral frequency-domain (PSFD) formulations for optical waveguides with arbitrary step-index profile is further implemented with the uniaxial perfectly matched layer (UPML) absorption boundary conditions for treating leaky waveguides and calculating their complex modal effective indices. The role of the UPML reflection coefficient in achieving high-accuracy mode solution results is particularly investigated. A six-air-hole microstructured fiber is analyzed as an example to compare with published high-accuracy multipole method results for both the real and imaginary parts of the effective indices.