Shedding light on disordered proteins
Disordered proteins often fold as they bind to a partner protein. There could be many different molecular trajectories between the unbound proteins and the bound ...complex. Most methods to measure transition paths rely on monitoring a single distance, making it difficult to resolve complex pathways. Kim and Chung used fast three-color single-molecule Foster resonance energy transfer (FRET) to simultaneously probe distance changes between the two ends of an unfolded protein and between each end and a probe on the partner protein. They show that binding can be initiated by diverse conformations and that the molecules are held together by non-native interactions as the disordered protein folds. This allows the association to be diffusion limited because most collisions lead to binding.
Science
, this issue p.
1253
Three-color single-molecule Förster resonance energy transfer reveals diverse binding transition paths of disordered proteins.
Transition paths of macromolecular conformational changes such as protein folding are predicted to be heterogeneous. However, experimental characterization of the diversity of transition paths is extremely challenging because it requires measuring more than one distance during individual transitions. In this work, we used fast three-color single-molecule Förster resonance energy transfer spectroscopy to obtain the distribution of binding transition paths of a disordered protein. About half of the transitions follow a path involving strong non-native electrostatic interactions, resulting in a transition time of 300 to 800 microseconds. The remaining half follow more diverse paths characterized by weaker electrostatic interactions and more than 10 times shorter transition path times. The chain flexibility and non-native interactions make diverse binding pathways possible, allowing disordered proteins to bind faster than folded proteins.
An electride, a generalized form of cavity-trapped interstitial anionic electrons (IAEs) in a positively charged lattice framework, shows exotic properties according to the size and geometry of the ...cavities. Here, we report that the IAEs in layer structured Gd
C
·2e
electride behave as ferromagnetic elements in two-dimensional interlayer space and possess their own magnetic moments of ~0.52 μ
per quasi-atomic IAE, which facilitate the exchange interactions between interlayer gadolinium atoms across IAEs, inducing the ferromagnetism in Gd
C
·2e
electride. The substitution of paramagnetic chlorine atoms for IAEs proves the magnetic nature of quasi-atomic IAEs through a transition from ferromagnetic Gd
C
·2e
to antiferromagnetic Gd
CCl caused by attenuating interatomic exchange interactions, consistent with theoretical calculations. These results confirm that quasi-atomic IAEs act as ferromagnetic elements and trigger ferromagnetic spin alignments within the antiferromagnetic Gd
C
lattice framework. These results present a broad opportunity to tailor intriguing ferromagnetism originating from quasi-atomic interstitial electrons in low-dimensional materials.
The c-fos gene (also known as Fos) is induced by a broad range of stimuli and is a reliable marker for neural activity. Its induction mechanism and available reporter mouse lines are based ...exclusively on c-fos promoter activity. Here we demonstrate that multiple enhancers surrounding the c-fos gene are crucial for ensuring robust c-fos response to various stimuli. Membrane depolarization, brain-derived neurotrophic factor (BDNF) and forskolin activate distinct subsets of the enhancers to induce c-fos transcription in neurons, suggesting that stimulus-specific combinatorial activation of multiple enhancers underlies the broad inducibility of the c-fos gene. Accordingly, the functional requirement of key transcription factors varies depending on the type of stimulation. Combinatorial enhancer activation also occurs in the brain. Providing a comprehensive picture of the c-fos induction mechanism beyond the minimal promoter, our study should help in understanding the physiological nature of c-fos induction in relation to neural activity and plasticity.
•SHPB tests for mortar and concrete with various aggregate sizes were performed.•Heterogeneity was negligible with aggregate smaller than a third of specimen size.•Pure rate DIFs varied along with ...maximum aggregate size, but there was no tendency.•A guide to maximum aggregate sizes for SHPB test specimens was suggested.
Dynamic increase factor (DIF) is a measure of the rate effect in the analysis and design of structures subjected to impact or impulsive loads. A variety of DIFs have been suggested based on the results of split Hopkinson pressure bar (SHPB) tests, which is the test technique most commonly used to obtain dynamic material properties. However, due to the lack of a standard test method and some limitations in the SHPB equipment, most SHPB tests have been conducted for mortar or concrete specimens containing small size coarse aggregate that is very different from the actual concrete used in construction. The DIFs that are provided in most structural design codes are based on these test results. Therefore, it is necessary to investigate the effect of coarse aggregate size on the dynamic concrete compressive strength. In this study, a series of SHPB tests were conducted for mortar and concrete specimens with various maximum aggregate sizes. The test results indicated that the larger maximum coarse aggregate sizes induce larger heterogeneity of specimens. On the other hand, the pure rate DIFs did not exhibit a dependency on the maximum coarse aggregate size. Based on these results, guidance as to the maximum coarse aggregate size of concrete specimens for SHPB tests is provided.
Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs ...facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons. eRNAs are synthesized prior to the culmination of target gene transcription and interact with the NELF complex. Knockdown of eRNAs expressed at neuronal enhancers impairs transient release of NELF from the specific target promoters during transcriptional activation, coinciding with a decrease in target mRNA induction. The enhancer-promoter interaction was unaffected by eRNA knockdown. Instead, chromatin looping might enable eRNAs to act locally at a specific promoter. Our findings highlight the spatiotemporally regulated action mechanism of eRNAs during early transcriptional elongation.
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•eRNAs play a modulatory role in the expression of neuronal immediate early genes•eRNAs facilitate NELF release from the target promoter•The interaction between NELF-E and eRNAs is dependent on the RRM domain•The activity-induced enhancer-promoter interaction does not require eRNAs
Transcription from enhancers produces eRNAs, but how eRNAs influence gene activation is unclear. Schaukowitch et al. show that eRNAs induce immediate early genes in neurons by facilitating the release of the negative elongation factor, NELF, from the promoter so that paused RNA polymerase II can engage in productive transcription.
•Strain acceleration and geometry of a specimen lead to inertia effects in SHPB test.•Concrete SHPB tests were performed.•DIF considering the pure rate effect was proposed.•Proposed DIF provided an ...accurate prediction for the apparent dynamic strength.
The dynamic increase factor (DIF) has been widely used to consider the rate effect in the analysis and design of concrete structures that are subject to impact loads. A variety of DIFs have been proposed by many researchers based on the results of dynamic material tests such as the split Hopkinson pressure bar (SHPB) test. These DIFs have been adopted in authoritative design guidelines and model codes such as the ACI 349–13, ACI 370R-14, fib MC2010, and UFC 3-340-02. However, previous studies did not properly consider the strain acceleration and the geometrical characteristics of the test specimens that cause the axial and radial inertia forces which influence the test results. For this reason, predictions can become non conservative when these DIFs are used in the analysis and design of concrete structures that are subject to impact or impulsive loads. In this study, to overcome the limitations of existing DIFs, a new concrete DIF that excludes inertia effects by considering the strain acceleration and geometry of the specimens has been proposed based on SHPB test results. The proposed DIF was numerically validated using finite element analyses. Compared with other existing DIFs, the results show improved predictions of the enhancement of the concrete compressive strength due to rate effect.
According to current paradigms, various risk factors, such as genetic mutations, oxidative stress, neural network dysfunction, and abnormal protein degradation, contribute to the progression of brain ...disorders. Through the cooperation of gene transcripts in biological processes, the study of noncoding RNAs can lead to insights into the cause and treatment of brain disorders. Recently, long noncoding RNAs (lncRNAs) which are longer than 200 nucleotides in length have been suggested as key factors in various brain disorders. Accumulating evidence suggests the potential of lncRNAs as diagnostic or prognostic biomarkers and therapeutic targets. High-throughput screening-based sequencing has been instrumental in identification of lncRNAs that demand new approaches to understanding the progression of brain disorders. In this review, we discuss the recent progress in the study of lncRNAs, and addresses the pathogenesis of brain disorders that involve lncRNAs and describes the associations of lncRNAs with neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and neurodevelopmental disorders. We also discuss potential targets of lncRNAs and their promise as novel therapeutics and biomarkers in brain disorders.
Taming electronic and thermal transport properties is the ultimate goal in the quest to achieve unprecedentedly high performance in thermoelectric (TE) materials. Most state‐of‐the‐art TE materials ...are inherently narrow bandgap semiconductors, which have an inevitable contribution from minority carriers, concurrently decreasing Seebeck coefficient and increasing thermal conductivity. Nevertheless, the restraint control of minority carrier transport is seldom considered as a key element to enhance the TE figure of merit (zT). Herein, it is verified that the localized dislocation arrays at grain boundaries enable the suppression of minority carrier contribution to electronic transport properties, resulting in an increase of the Seebeck coefficient and the carrier mobility in bismuth antimony tellurides. It is also suggested that the suppression of minority carriers via the generation of dislocation arrays at grain boundaries is an effective and noninvasive strategy to optimize overall electronic transport properties without sacrificing predominant characteristics of majority carriers in TE materials.
The localized dislocation arrays at grain boundaries enable the selective suppression of minority carrier contribution to electronic transport properties without sacrificing characteristics of majority carriers, resulting in an increase of overall Seebeck coefficient and carrier mobility in bismuth antimony tellurides. This finding provides an effective and noninvasive paradigm to optimize electronic transport properties of conventional thermoelectric materials.
Intrinsically disordered proteins (IDPs) usually fold during binding to target proteins. In contrast to interactions between folded proteins, this additional folding step makes the binding process ...more complex. Understanding the mechanism of coupled binding and folding of IDPs requires analysis of binding pathways that involve formation of the transient complex (TC). However, experimental characterization of TC is challenging because it only appears for a very brief period during binding. Here, we use single-molecule fluorescence spectroscopy to investigate the mechanism of diffusion-limited association of an IDP. A large enhancement of the association rate is observed due to the stabilization of TC by non-native electrostatic interactions. Moreover, photon-by-photon analysis reveals that the lifetime of TC for IDP binding is at least two orders of magnitude longer than that for binding of two folded proteins. This result suggests the long lifetime of TC is generally required for folding of IDPs during binding processes.
Hydroxypropyl methylcellulose (HPMC) was combined with oregano essential oil nanoemulsion (ORNE) at concentrations of 0–7.5% (v/v) to produce active composite films. The mechanical, optical, water ...vapour barrier, antimicrobial, and antioxidant properties of the composite films were evaluated. The composite films containing 5.0% (v/v) ORNE showed increased elongation at break compared to the control films, although their tensile strength and Young's modulus were lower. In addition, these composite films showed greater opacity and decreased UV and water vapour transmittance, indicating that incorporation of ORNE resulted in enhanced barrier properties. Furthermore, the composite films were effective against all tested bacterial strains, particularly against Salmonella typhimurium, as evidenced by the large inhibition zone attained (47.5 mm) in the disc diffusion test. Antioxidant activity was assessed by the DPPH and ABTS assays, with the composite films containing 5.0% (v/v) ORNE showing values approximately 69% and 46% higher than those of the control, respectively. Therefore, the developed composite films could potentially be used as active packaging with antibacterial and antioxidant properties.
•HPMC films incorporating oregano essential oil nanoemulsions were prepared.•The films showed excellent antibacterial effects, particularly against S. typhimurium.•DPPH and ABTS assays revealed the antioxidant properties of the films.•The films also showed enhanced UV and water vapour barrier properties.
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