scholarly journals Is the H4 histone tail intrinsically disordered or intrinsically multifunctional?

2021 ◽  
Vol 23 (9) ◽  
pp. 5134-5142
Author(s):  
Konstantin Röder

While the H4 histone tail exhibits a large structural variance associated with disorder, the energy landscape shows a high level of topographic order. This result opens a new perspective on how we interpret disorder.

2021 ◽  
Author(s):  
Jimei Han ◽  
Lianhong Gu ◽  
Jeffrey M Warren ◽  
Anirban Guha ◽  
David A Mclennan ◽  
...  

Abstract The induction and relaxation of photochemistry and non-photochemical quenching (NPQ) are not instantaneous and require time to respond to fluctuating environments. There is a lack of integrated understanding on how photochemistry and NPQ influence photosynthesis in fluctuating environments. We measured the induction and relaxation of chlorophyll a fluorescence and gas exchange in poplar and cotton at varying temperatures under saturating and fluctuating lights. When the light shifted from dark to high, the fraction of open reaction centers in photosystem II (qL) gradually increased while NPQ increased suddenly and then remained stable. Temperature significantly changed the response of qL but not that of NPQ during the dark to high light transition. Increased qL led to higher photosynthesis but their precise relationship was affected by NPQ and temperature. qL was significantly related to biochemical capacity. Thus, qL appears to be a strong indicator of the activation of carboxylase, leading to the similar dynamics between qL and photosynthesis. When the light shifted from high to low intensity, NPQ is still engaged at a high level, causing a stronger decline in photosynthesis. Our finding suggests that the dynamic effects of photochemistry and NPQ on photosynthesis depend on the phases of environmental fluctuations and interactive effects of light and temperature. Across the full spectra of light fluctuation, the slow induction of qL is a more important limiting factor than the slow relaxation of NPQ for photosynthesis in typical ranges of temperature for photosynthesis. The findings provided a new perspective to improve photosynthetic productivity with molecular biology under natural fluctuating environments.


2019 ◽  
Author(s):  
A. M. Khalili

The dream of building machines that have human-level intelligence has inspired scientists for decades. Remarkable advances have been made recently; however, we are still far from achieving this goal. In this paper, I propose an alternative perspective on how these machines might be built focusing on the scientific discovery process which represents one of our highest abilities that requires a high level of reasoning and remarkable problem-solving ability. By trying to replicate the procedures followed by many scientists, the basic idea of the proposed approach is to use a set of principles to solve problems and discover new knowledge. These principles are extracted from different historical examples of scientific discoveries. Building machines that fully incorporate these principles in an automated way might open the doors for many advancements.


2020 ◽  
Vol 73 (7) ◽  
pp. 1480-1483
Author(s):  
Tetyana O. Pertseva ◽  
Lyudmyla I. Konopkina ◽  
Alina O. Babenko

The aim: The aim of the research was to analyze the results of observation and examination of COPD patients in order to identify a group of individuals with potential asthma overlap. Materials and methods: We have conducted a two-stage dynamic investigation of 43 COPD patients during 3–8 years. The patients were divided into two groups: group 1 counted 30 individuals who presented with at least one episode of reversible bronchial obstruction (RBO) during the observation; group 2 – 13 individuals who presented with nonreversible bronchial obstruction (nonRBO). At the first stage, we conducted a clinical observations analysis and studied lung function examination records; at the second stage, we calculated the markers of allergic inflammation. Results: It was revealed that around 70% of COPD patients have occasional episodes of RBO. It was established that the level of blood eosinophils in these patients on the whole is rather low even in people with intermittent RBO, and the total IgE level appeared to be significantly higher in patients with intermittent RBO comparing to the level of this marker in patients who have nonRBO. Conclusions: COPD patients with intermittent RBO and high level of total IgE level form a group with potential asthma overlap.


2016 ◽  
Vol 2 (1) ◽  
pp. 29-44 ◽  
Author(s):  
Fang Wang ◽  
Yaoyao Peng ◽  
Hsiao Chieh Wang ◽  
Fan Yin

Purpose – Ancient city walls are typical linear space elements of Beijing that represent the transformation of urban form over the past 800 years and have greatly influenced the memory of the entire city. However, recently, most of the walls have been torn down in the process of fast urbanization and old city renewal. The purpose of this paper is to focus on people’s cognition and evaluation of urban memory during this pull-down-and-preserve process. Design/methodology/approach – A sample of 380 participants was investigated on a number of issues using questionnaires, including memory case reminders (stability, variability, temporality), emotional bonding with memory case (identity, dependence, authenticity), and socio-demographic variables (age, education, life experience, length of residence). The urban memory cognition model and attitude evaluation value model which were based on Likert scale were used to process the collected data. Findings – In the three aspects of memory case reminders, stability and temporary elements can be most cognized, whereas variability elements are more difficult due to their change over time. As for emotional bonding with memory case, people show a high level of identification with the walls; the walls’ memory being passed down could enhance people’s memory when mentioning Beijing. Further, higher education groups consider the walls’ authenticity to be most important and are unwilling to accept the outcome of walls-ruins parks; older adults have tolerant attitudes to the ruins parks. Originality/value – This study could not only contribute to the excavation of urban memory, but also strengthen citizens’ sense of identity and cohesiveness, thus shaping the spirit and culture of the city. Some findings could provide applicable guidelines for urban heritage protection and contribute a new perspective on the interrelationship between people and their physical surroundings.


Author(s):  
Vladimir Lebedev ◽  
Sergey Stefanovsky ◽  
Alexander Kobelev ◽  
Fyodor Lifanov ◽  
Sergey Dmitriev

Results of feasibility tests of application of Cold Crucible Inductive Melting (CCIM) technology to high level waste (HLW) treatment on examples of Savannah River Site, USA, and PA “Mayak”, Russia, HLW, carried out at SIA Radon, and results of design of new perspective bench-scale HLW vitrification facility are presented in this report. Full-scale low level waste (LLW) vitrification plant is under operation at Radon since 2003. Successful Radon experience aroused an interest to this technology from US DOE. Since 2001 Radon performed tests on vitrification of surrogates of various types of HLW stored at US DOE Sites. Process variables were determined and vitrified wastes were characterized in details. Since 2007 Radon was a subcontractor in the project on design and construction of a new CCIM based vitrification facility at PA “Mayak”. From preliminary tests on Mayak HLW surrogates the main technological features of CCIM process were determined and principles of the process control were formulated. Radon performed the design of the cold crucible and automated control system. On the base of analysis of previously and newly obtained data the main requirements to designing of cold crucible melters and auxiliary equipment, intended for actual HLW treatment, were worked out.


2020 ◽  
Vol 1 (2) ◽  
pp. p77
Author(s):  
Cheng Zhan

This paper presents the findings of a corpus-based empirical study on the role of government staff interpreters in the political context of China. Based on a qualitative analysis of discourse documented in authentic encounters between top leaders of Guangdong Province and their foreign visitors in interpreter-facilitated communication, the paper attempts to question the long-held view that government staff interpreters serve as a neutral, transparent non-person. To provide perhaps a new perspective from which the interpreter’s role may be revisited, this paper looks at personal angle shifts in the interpretation done by six staff interpreters of Guangdong Foreign Affairs Office, including shifts between first person and third person angles, and second person and third person angles. With what corpus data reveal, the paper argues that the interpreter’s role as a mediator is conspicuous even in high-level political interpreting. Rather than a transparent non-person, the interpreter constructs and represents her identity as well as the identity of the institution she belongs to by discursive means, and therefore acts as an active party of communication.


2021 ◽  
Author(s):  
Murilo N Sanches ◽  
Kaitlin Knapp ◽  
Antonio Bento Oliveira Junior ◽  
Peter G Wolynes ◽  
Jose N Onuchic ◽  
...  

The amyloid-β (Aβ) monomer, an intrinsically disordered peptide, is produced by the cleavage of the amyloid precursor protein, leading to Aβ40 and Aβ42 as major products. These two isoforms generate pathological aggregates, whose accumulation correlates with Alzheimer's disease (AD). Experiments have shown that even though the natural abundance of Aβ42 is smaller than that for Aβ40, the Aβ42 is more aggregation-prone compared to Aβ40. Moreover, several single-point mutations are associated with early-onset forms of AD. This work analyzes coarse-grained AWSEM simulations of normal Aβ40 and Aβ42 monomers, along with six single-point mutations associated with early on set disease. We analyzed the simulations using the Energy Landscape Visualization Method (ELViM), a reaction coordinate-free approach suited to explore the frustrated energy landscapes of intrinsically disordered proteins. ELViM is shown to distinguish the monomer ensembles of variants that rapidly form fibers from those that do not form fibers as readily. It also delineates the amino-acid contacts characterizing each ensemble. The results shed light on the potential of ELViM to probe intrinsically disordered proteins.


2021 ◽  
Author(s):  
Antonio B. Oliveira ◽  
Xingcheng Lin ◽  
Prakash Kulkarni ◽  
José N. Onuchic ◽  
Susmita Roy ◽  
...  

AbstractIntrinsically disordered proteins (IDPs) lack a rigid 3D structure and populate a polymorphic ensemble of conformations. Because of the lack of a reference conformation, their energy landscape representation in terms of reaction coordinates presents a daunting challenge. Here, our newly developed Energy Landscape Visualization Method (ELViM), a reaction coordinate-free approach, shows its prime application to explore frustrated energy landscapes of an intrinsically disordered protein, Prostate-Associated Gene 4 (PAGE4). PAGE4 is a transcriptional coactivator that potentiates the oncogene c-Jun. Two kinases, namely HIPK1 and CLK2, phosphorylate PAGE4 generating variants phosphorylated at different serine/threonine residues (HIPK1-PAGE4 and CLK2-PAGE4, respectively) with opposing functions. While HIPK1-PAGE4 predominantly phosphorylates Thr51 and potentiates c-Jun, CLK2-PAGE4 hyper-phosphorylates PAGE4 and attenuates transactivation. To understand the underlying mechanisms of conformational diversity among different phosphoforms, we have analyzed their atomistic trajectories simulated using AWSEM forcefield and the energy landscapes were elucidated using ELViM. This method allows us to identify and compare the population distributions of different conformational ensembles of PAGE4 phosphoforms using the same effective phase space. The results reveal a predominant conformational ensemble with an extended C-terminal segment of WT PAGE4, which exposes a functional residue Thr51, implying its potential of undertaking a fly-casting mechanism while binding to its cognate partner. In contrast, for HIPK1-PAGE4, a compact conformational ensemble enhances its population sequestering phosphorylated-Thr51. This clearly explains the experimentally observed weaker affinity of HIPK1-PAGE4 for c-Jun. ELViM appears as a powerful tool especially to analyze the highly-frustrated energy landscape representation of IDPs where appropriate reaction coordinates are hard to apprehend.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Song-Ho Chong ◽  
Sihyun Ham

Abstract Folding funnel is the essential concept of the free energy landscape for ordered proteins. How does this concept apply to intrinsically disordered proteins (IDPs)? Here, we address this fundamental question through the explicit characterization of the free energy landscapes of the representative α-helical (HP-35) and β-sheet (WW domain) proteins and of an IDP (pKID) that folds upon binding to its partner (KIX). We demonstrate that HP-35 and WW domain indeed exhibit the steep folding funnel: the landscape slope for these proteins is ca. −50 kcal/mol, meaning that the free energy decreases by ~5 kcal/mol upon the formation of 10% native contacts. On the other hand, the landscape of pKID is funneled but considerably shallower (slope of −24 kcal/mol), which explains why pKID is disordered in free environments. Upon binding to KIX, the landscape of pKID now becomes significantly steep (slope of −54 kcal/mol), which enables otherwise disordered pKID to fold. We also show that it is the pKID–KIX intermolecular interactions originating from hydrophobic residues that mainly confer the steep folding funnel. The present work not only provides the quantitative characterization of the protein folding free energy landscape, but also establishes the usefulness of the folding funnel concept to IDPs.


Author(s):  
Meishu Zhang ◽  
Yu Jia ◽  
Nianxin Wang ◽  
Shilun Ge

In China, it has long become imperative for the management of education and science and technology to build high-level scientific and technological innovation teams. Scientifically and accurately identifying core scientific research teams is an important condition for cultivating and building such teams. The absolute threshold method (e.g., c-level clique at, n- clique, k-core) is the prevailing means of identifying core teams and their core members. In fact, effects such as “the preference-dependent effect”, “the apostle effect” and “the star effect”, the cooperative relationship between the researchers is not even. This study, based on the co-authorship network, found that not choosing the absolute threshold properly can easily lead to poor identification of core members of some teams. Even worse, when the absolute threshold is too large, this “uniform” evaluation criterion of tie strength results in the elimination of some core teams in some disciplines. This paper uses relative tie strength to identify core scientific research teams from a new perspective, which can effectively avoid the situation of some core team members being ignored because of the mandatory requirements of the absolute tie strength among members, and can also solve the challenge of threshold selections for identifying different teams.


Sign in / Sign up

Export Citation Format

Share Document