Histone acylation marks respond to metabolic perturbations and enable cellular adaptation

Acetylation is the most studied histone acyl modification and has been recognized as a fundamental player in metabolic gene regulation, whereas other short-chain acyl modifications have only been recently identified, and little is known about their dynamics or molecular functions at the intersection of metabolism and epigenetic gene regulation. In this study, we aimed to understand the link between nonacetyl histone acyl modification, metabolic transcriptional regulation, and cellular adaptation. Using antibodies specific for butyrylated, propionylated, and crotonylated H3K23, we analyzed dynamic changes of H3K23 acylation upon various metabolic challenges. Here, we show that H3K23 modifications were highly responsive and reversibly regulated by nutrient availability. These modifications were commonly downregulated by the depletion of glucose and recovered based on glucose or fatty acid availability. Depletion of metabolic enzymes, namely, ATP citrate lyase, carnitine acetyltransferase, and acetyl-CoA synthetase, which are involved in Ac-CoA synthesis, resulted in global loss of H3K23 butyrylation, crotonylation, propionylation, and acetylation, with a profound impact on gene expression and cellular metabolic states. Our data indicate that Ac-CoA/CoA and central metabolic inputs are important for the maintenance of histone acylation. Additionally, genome-wide analysis revealed that acyl modifications are associated with gene activation. Our study shows that histone acylation acts as an immediate and reversible metabolic sensor enabling cellular adaptation to metabolic stress by reprogramming gene expression. © 2020, The Author(s).1

Liver-Specific Deletion of Mouse CTCF Leads to Hepatic Steatosis via Augmented PPARγ Signaling

Background & Aims: The liver is the major organ for metabolizing lipids, and malfunction of the liver leads to various diseases. Nonalcoholic fatty liver disease is rapidly becoming a major health concern worldwide and is characterized by abnormal retention of excess lipids in the liver. CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein that regulates higher-order chromatin organization and is involved in various gene regulation processes. Here, we sought to determine the physiological role of CTCF in hepatic lipid metabolism. Methods: We generated liver-specific, CTCF-ablated and/or CD36 whole-body knockout mice. Overexpression or knockdown of peroxisome proliferator-activated receptor (PPAR)γ in the liver was achieved using adenovirus. Mice were examined for development of hepatic steatosis and inflammation. RNA sequencing was performed to identify genes affected by CTCF depletion. Genome-wide occupancy of H3K27 acetylation, PPARγ, and CTCF were analyzed by chromatin immunoprecipitation sequencing. Genome-wide chromatin interactions were analyzed by in situ Hi-C. Results: Liver-specific, CTCF-deficient mice developed hepatic steatosis and inflammation when fed a standard chow diet. Global analysis of the transcriptome and enhancer landscape revealed that CTCF-depleted liver showed enhanced accumulation of PPARγ in the nucleus, which leads to increased expression of its downstream target genes, including fat storage-related gene CD36, which is involved in the lipid metabolic process. Hepatic steatosis developed in liver-specific, CTCF-deficient mice was ameliorated by repression of PPARγ via pharmacologic blockade or adenovirus-mediated knockdown, but hardly rescued by additional knockout of CD36. Conclusions: Our data indicate that liver-specific deletion of CTCF leads to hepatosteatosis through augmented PPARγ DNA-binding activity, which up-regulates its downstream target genes associated with the lipid metabolic process. © 2021 The Authors1

항비만 화합물에 의한 식욕조절 및 대사 프로파일 연구

anti-obesity compound; obesity; diabetes; hexamethylene bisacetamide; appetite control; hypothalamus; neuropeptide; glucagon-like peptide-1; liraglutide; metabolomics; metabolic alteration; plasma; liver; skeletal muscleDoctordCollectio

Metamaterials and chiral sensing: a review of fundamentals and applications

Chirality, a property of broken mirror symmetry, prevails in nature. Chiral molecules show different biochemical behaviors to their mirror molecules. For left or right circularly polarized lights, the fundamental chiral states of electromagnetic fields interact differently with chiral matter, and this effect has been used as a powerful tool for the detection of chiral molecules. This optical sensing, also termed chiral sensing, is not only easy to implement but also non-invasive to the analytes. However, the measurements made by the optical sensing of chiral molecules are challenging, as chiroptical signals are extremely weak. Recent years have seen active research efforts into metamaterial and plasmonic platforms for manipulating local fields to enhance chiroptical signals. This metamaterial approach offers new possibilities of chiral sensing with high sensitivity. Here, we review the recent advances in chiral sensing using metamaterial and plasmonic platforms. In addition, we explain the underlying principles behind the enhancement of chiroptical signals and highlight practically efficient chiral sensing platforms. We also provide perspectives that shed light on design considerations for chiral sensing metamaterials and discuss the possibility of other types of chiral sensing based on resonant metamaterials

A Metabolomic Approach to Understanding the Metabolic Link between Obesity and Diabetes

Obesity and diabetes arise from an intricate interplay between both genetic and environmental factors. It is well recognized that obesity plays an important role in the development of insulin resistance and diabetes. Yet, the exact mechanism of the connection between obesity and diabetes is still not completely understood. Metabolomics is an analytical approach that aims to detect and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics to the identification of disease biomarkers, with a number of well-known biomarkers identified. Metabolomics is a potent approach to unravel the intricate relationships between metabolism, obesity and progression to diabetes and, at the same time, has potential as a clinical tool for risk evaluation and monitoring of disease. Moreover, metabolomics applications have revealed alterations in the levels of metabolites related to obesity-associated diabetes. This review focuses on the part that metabolomics has played in elucidating the roles of metabolites in the regulation of systemic metabolism relevant to obesity and diabetes. It also explains the possible metabolic relation and association between the two diseases. The metabolites with altered profiles in individual disorders and those that are specifically and similarly altered in both disorders are classified, categorized and summarized. © The Korean Society for Molecular and Cellular Biology.TRU

Field Experiments to Evaluate Thermal Performance of Energy Slabs with Different Installation Conditions

The energy slab is a novel type of horizontal Ground Heat Exchanger (GHEX), where heat exchange pipes are encased in building slab structures. The thermal performance of energy slabs is usually inferior to the conventional closed-loop vertical GHEX because its installation depth is relatively shallow and therefore affected by ambient air temperature. In this paper, heat exchange pipes were made of not only conventional high-density polyethylene (HDPE), but also stainless steel (STS), which is expected to enhance the thermal performance of the energy slabs. In addition to a floor slab, a side wall slab was also used as a component of energy slabs to maximize the use of geothermal energy that can be generated from the underground space. Moreover, a thermal insulation layer in the energy slabs was considered in order to reduce thermal interference induced by ambient air temperature. Consequently, two different field-scale energy slabs (i.e., floor-type and wall-type energy slabs) were constructed in a test bed, and two types of heat exchange pipes (i.e., STS pipe and HDPE pipes) were installed in each energy slab. A series of thermal response tests (TRTs) and thermal performance tests (TPTs) were conducted to evaluate the heat exchange performance of the constructed energy slabs. Use of the STS heat exchange pipe enhanced the thermal performance of energy slabs. Additionally, the wall-type energy slab had a similar thermal performance to the floor-type energy slab, which infers the applicability of the additional use of the wall-type energy slab. Note that if an energy slab is not thermally cut off from the building’s interior space with the aid of thermal insulation layers, heat exchange within the energy slabs should be significantly influenced by fluctuations in ambient temperature

Microscopic Origin of Surface-Enhanced Circular Dichroism

Circular dichroism (CD), the difference in absorption of two opposite circularly polarized light sources by chiral molecules, can be significantly enhanced when molecules are adsorbed on the surface of nanostructures. We present a theory based on Poynting’s theorem adapted for chiral media to analyze the surface-enhanced CD of a chiral molecule/nanostructure coupled system. Our theory clarifies the microscopic origin of surface-enhanced CD signals by showing that the enhanced CD has two forms, inherent and induced. The inherent CD is the direct molecular CD that becomes enhanced due to the strongly localized optical helicity density near the nanostructure. The induced CD, previously ignored, derives from asymmetric excitation and absorption of electromagnetic fields inside the nanostructures surrounded by chiral molecules upon the injection of two oppositely circularly polarized light sources. Moreover, it is demonstrated that the induced CD can contribute significantly to the CD signals measured by surface-enhanced chiroptical spectroscopy

Field-induced nucleation in threshold switching characteristics of electrochemical metallization devices

In this research, we investigate electrically driven threshold switching (TS) characteristics in electrochemical metallization cells by adopting the field-induced nucleation theory. For this aim, Ag/HfO2 and Ag/TiO2 based TS devices are prepared and examined. First, we carry out the field driven turn-on process to form Ag filaments created as a consequence of sequential nucleation of Ag ions from the bottom electrode. During the filament formation process, it is observed that the prepared devices show switching time exponential in voltage and temperature with different nucleation barrier energies (W-0), which confirms the field-induced nucleation theory. Furthermore, we find that the device with higher W-0 shows faster dissolution speed. This implies that the slow turn-off speed of the TS device can be improved by finding a material system with a higher W-0 value. Published by AIP Publishing.116sciescopu

Measuring the optical permittivity of two-dimensional materials without a priori knowledge of electronic transitions

We propose a deterministic method to measure the optical permittivity of two-dimensional (2D) materials without a priori knowledge of the electronic transitions over the spectral window of interest. Using the thin-film approximation, we show that the ratio of reflection coefficients for s and p polarization can give a unique solution to the permittivity of 2D materials within the measured spectral window. The uniqueness and completeness of our permittivity measurement method do not require a priori knowledge of the electronic transitions of a given material. We experimentally demonstrate that the permittivity of monolayers of MoS2, WS2, and WSe2 in the visible frequency range can be accurately obtained by our method. We believe that our method can provide fast and reliable measurement of the optical permittivity of newly discovered 2D materials