Acetylation of histones at DNA regulatory elements plays a critical role in transcriptional activation. Histones are also modified by other acyl moieties, including crotonyl, yet the mechanisms that ...govern acetylation versus crotonylation and the functional consequences of this “choice” remain unclear. We show that the coactivator p300 has both crotonyltransferase and acetyltransferase activities, and that p300-catalyzed histone crotonylation directly stimulates transcription to a greater degree than histone acetylation. Levels of histone crotonylation are regulated by the cellular concentration of crotonyl-CoA, which can be altered through genetic and environmental perturbations. In a cell-based model of transcriptional activation, increasing or decreasing the cellular concentration of crotonyl-CoA leads to enhanced or diminished gene expression, respectively, which correlates with the levels of histone crotonylation flanking the regulatory elements of activated genes. Our findings support a general principle wherein differential histone acylation (i.e., acetylation versus crotonylation) couples cellular metabolism to the regulation of gene expression.
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•The histone acetyltransferase p300 also regulates histone crotonylation•Histone crotonylation directly stimulates transcription•Histone crotonylation is regulated by the concentration of crotonyl-CoA•Local changes in differential histone acylation influence gene expression
Sabari et al. establish a direct role for histone crotonylation in the stimulation of transcription and demonstrate that the modification is regulated enzymatically by p300/CBP and metabolically by the availability of crotonyl-CoA.
Smart displays have been integrated into our daily life, providing new concepts of interconnections between humans and interactivity with close collaboration between users. As a centerpiece of this ...integration, textile displays that can be worn like clothes are being intensively developed and are poised to provide a more intimate and closer connection. Among various light sources that have been used in the field of textile displays, organic light‐emitting diodes (OLEDs) have attracted considerable attention as one of the promising candidates for realizing truly wearable textile displays (i.e., wearing displays) in that they have shown the highest level of technical maturity, including high optoelectronic performance and flexibility, which can provide not only clear visual information and versatility regardless of the surrounding environment but have also been industrially proven. This review introduces the recent progress in OLED‐based textile displays and related technologies, with the discussion of challenges and limitations of the fiber‐ and fabric‐based approaches. Additionally, specific opinions are provided on research opportunities for organic light‐emitting textile displays, which can contribute to realizing truly wearable textile displays with a complete platform in the future.
In this paper, we discuss approaches, including those for fiber and fabric, for realizing organic light‐emitting textile displays, their challenges, and recent progress in related display technologies including thin film transistors and encapsulation techniques. In addition, based on the progress, breakthroughs, and comprehensive reviews, opportunities for future research are discussed.
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral ...organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
Drosophila melanogaster is an ideal model to study Fragile X syndrome (FXS) as it presents us with a toolbox to identify genetic modifiers and to investigate the molecular mechanisms of FXS. Here we ...describe some of the methods that have been used to study FXS, ranging from reverse genetic screening using the GAL4-UAS system, to mushroom body staining and courtship behavioral assays to examine the learning and memory deficits associated with FXS.
Increasing demand for real-time healthcare monitoring is leading to advances in thin and flexible optoelectronic device-based wearable pulse oximetry. Most previous studies have used OLEDs for this ...purpose, but did not consider the side effects of broad full-width half-maximum (FWHM) characteristics and single substrates. In this study, we performed SpO
measurement using a fiber-based quantum-dot pulse oximetry (FQPO) system capable of mass production with a transferable encapsulation technique, and a narrow FWHM of about 30 nm. Based on analyses we determined that uniform angular narrow FWHM-based light sources are important for accurate SpO
measurements through multi-layer structures and human skin tissues. The FQPO was shown to have improved photoplethysmogram (PPG) signal sensitivity with no waveguide-mode noise signal, as is typically generated when using a single substrate (30-50%). We successfully demonstrate improved SpO
measurement accuracy as well as all-in-one clothing-type pulse oximetry with FQPO.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (
). FXTAS is ...characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and
models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat
mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells. Besides these CGG-mediated mechanisms, recent studies have shed light on additional mechanisms of pathogenesis, such as the antisense transcript
, mitochondrial dysfunction, DNA damage from R-loop formation and 5-hydroxymethylcytosine (5hmC)-mediated epigenetic modulation. Here we summarize the recent progress towards understanding the etiology of FXTAS and provide an overview of potential treatment strategies.
Cover Image, Volume 30, Issue 10 Hwang, Yong Ha; Kong, Seong Uk; Kim, Chan Young ...
Journal of the Society for Information Display,
October 2022, 2022-10-00, 20221001, Volume:
30, Issue:
10
Journal Article
The cover image is based on the Research Article Organic Light‐Emitting Fibers and Fabrics for Truly Wearable Smart Displays: Recent Progress and Future Opportunities by Yong Ha Hwang et al., ...https://doi.org/10.1002/jsid.1164.
Anti-lipopolysaccharide factors (ALFs) are a representative host defense protein in crustaceans. In this study, we successfully developed two novel antimicrobial peptides (AMPs), named crab-ALF2A and ...crab-ALF6A, which contain changes to the amino acid sequences of the lipopolysaccharide binding domain and signal peptide, respectively, of the ALF of the swimming crab Portunus trituberculatus. The crab-ALF2A peptide showed potent antimicrobial activity against the Gram-positive bacteria Bacillus cereus, Staphylococcus aureus, and Streptococcus iniae (minimal effective concentration MEC 1.51–1.93 μg/mL) and the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli (MEC 1.87–1.98 μg/mL), with maximal bactericidal activity at a peptide concentration of 5 μg/mL. The crab-ALF6A peptide also showed potent antimicrobial activity against B. cereus, S. aureus, and S. iniae (MEC 1.49–2.3 μg/mL) and P. aeruginosa and E. coli (MEC 1.72–1.19 μg/mL) at a peptide concentration of 5 μg/mL. Notably, the crab-ALF2A and crab-ALF6A peptides exhibited strong activity against Candida albicans (MECs of 2.11 and 1.95 μg/mL, respectively). These activities were stable following heat treatment. Moreover, the effect of crab-ALF2A and crab-ALF6A peptide treatment on microbe cell morphology was confirmed by scanning electron microscopy. Membrane disruption and damage, and the leakage of cytoplasmic content were clearly observed. A downsizing peptide approach illustrated that the hexapeptide ALF6A8 (RVLLRL) was the shortest peptide showing significant antimicrobial activity. Our approach allows for the generation of novel antimicrobial peptides in a cost effective manner as potential next-generation antibiotics.
•Novel antimicrobial peptides were designed based on the anti-LPS factor of Portunus tribuberculatus.•Membrane disruption and damage of microbes by AMPs were all clearly observed by scanning electron microscopy.•The hexapeptide (ALF6A8) was the shortest analogous form showing significant antimicrobial activity.
Measures of pruritus severity and quality of life (QoL) are necessary for the development of therapeutics for children with chronic pruritus. In children, questionnaires need to be developed for ...specific age groups given the differences in cognitive levels. In this study, we aimed to develop tools to assess QoL and pruritus severity in children 6 to 7-years-old with chronic pruritus.
Based on open interviews with children, we developed a cartoon-annotated QoL instrument, KidsItchyQoL, and validated an existing pruritus severity instrument, ItchyQuant, that measures pruritus impact and severity for the preceding week. Both instruments were administered to 100 children aged 6-7 years with chronic pruritus. The data were analyzed for reliability, reproducibility, construct validity, and responsiveness.
We found the 14-item KidsItchyQoL to be reliable (Cronbach's α = 0.846) and reproducible (intraclass correlation coefficient (ICC) = 0.66) as was the ItchyQuant (ICC = 0.47). With respect to construct validity, examination of eigenvalues of the inter-item polychoric correlation matrix suggested three dominant factors. A subsequent confirmatory factor analysis suggested that a 3-dimensional simple structure model with correlated factors provided a reasonable data representation. The responsiveness of KidsItchyQoL and ItchyQuant (P = .005, GLM procedure) were demonstrated with scores changing as expected with the self-reported change of itch severity.
These results demonstrate promise for a new set of reliable research tools to assess QoL and pruritus severity in children 6 to 7 years of age.