bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and mechanistic insights into the DNA glycosylase AAG-mediated base excision in nucleosome
Authors: Zheng Lvqin , Tsai Bin , Gao Ning 
Published: June 2022

AbstractDNA glycosylase engaging with damaged base marks the initiation of base excision repair. Nucleosome-based packaging of eukaryotic genome obstructs DNA accessibility, and how DNA glycosylases locate the substrate site on nucleosomes is currently unclear. Here, we report cryo-electron microscopy structures of nucleosomes bearing a deoxyinosine (DI) in various geometric positions and structures of them in complex with DNA glycosylase AAG. The apo nucleosome structures show that the presence of a deoxyinosine alone perturbs nucleosomal DNA globally, leading to a general weakening of the interface between DNA and the histone core and a greater flexibility to the exit/entry of the nucleosomal DNA. AAG makes use of this nucleosomal plasticity and imposes further local deformation of the DNA through the formation of the stable enzyme-substrate complex. Mechanistically, local distortion augment, translation/rotational register shift and partial opening of the nucleosome are employed by AAG to cope with substrate sites in fully exposed, occluded and complete buried positions, respectively. Our findings reveal the molecular basis for the DI-induced modification on the structural dynamics of the nucleosome and elucidate how DNA glycosylase AAG accesses damaged sites on the nucleosome with different solution accessibility.
Schedule-dependent production of stereotyped sequences of actions
Authors: Follman Emma G. , Chevée Maxime , Kim Courtney J. , Johnson Amy R. , Tat Jennifer , Calipari Erin S. 
Published: June 2022

AbstractConcatenating actions into automatic routines is evolutionarily advantageous as it allows organisms to efficiently use time and energy under predictable conditions. However, over reliance on inflexible behaviors can be life-threatening in a changing environment and can become pathological in disease states such as obsessive-compulsive disorder (OCD) and substance use disorder (SUD). Understanding the conditions under which stereotypical sequences of actions are produced is crucial to studying how these behaviors can become maladaptive. Here, we investigated the ability of operant conditioning schedules and contingencies to promote reproducible sequences of five lever presses. We found that signaling reinforcer delivery with a visual cue was effective at increasing learning rates but resulted in mice pressing the lever in fast succession until the cue turned on, rather than pressing it five times. We also found that requiring mice to collect their reinforcer between sequences had little effect on both rate of behavior and on quantitative metrics of reproducibility such as interresponse interval (IRI) variance, and that a training strategy that directly reinforced sequences with low variance IRIs was not more effective than a traditional fixed ratio schedule at promoting reproducible action execution. Together, our findings provide insights into the parameters of behavioral training that promote reproducible sequences and serve as a roadmap to investigating the neural substrates of automatic behaviors.
Columnar scale lesions in barrel cortex degrade tactile discrimination but not detection
Authors: Ryan Lauren , Laughton Maya , Sun-Yan Andrew , Pancholi Ravi , Peron Simon 
Published: June 2022

AbstractPrimary sensory cortices typically display functional topography, suggesting that even small cortical volumes may underpin perception of specific stimuli. Because traditional loss-of-function approaches have a relatively large radius of effect (>1 mm), the behavioral necessity of smaller cortical volumes remains unclear. In the mouse primary vibrissal somatosensory cortex (vS1), ‘barrels’ with a radius of ∼150 μm receive input predominantly from a single whisker, partitioning vS1 into a topographic map of well-defined columns. Here, we train animals implanted with a cranial window over vS1 to perform single-whisker perceptual tasks. We then use high-power laser exposure centered on the barrel representing the spared whisker to produce lesions with an average volume of ∼2 barrels. These columnar scale lesions impair performance on object location discrimination tasks without disrupting vibrissal kinematics. Animals with degraded discrimination performance can immediately perform a detection task with high accuracy. Animals trained de novo on both simple and complex detection tasks showed no behavioral deficits following columnar scale lesions. Thus, vS1 barrels are necessary for performing object location discrimination but not simple or complex object detection behaviors.
CDK6 activity in a recurring convergent kinase network motif
Authors: Gangemi Christina , Sabapathy Rahkesh T , Janovjak Harald 
Published: June 2022

ABSTRACTMore than 500 kinases phosphorylate ∼15% of all human proteins. The architecture of the phosphorylation network has been studied extensively, for instance to compile global interaction maps, trace signal transduction pathways or identify chemical intervention points. In contrast, systematic investigation of local motifs is rare but may provide a complementary understanding of network and kinase function. Here, we report on the occurrence, topology and experimental analysis of convergent kinase-substrate relationships (cKSRs) in which ≥two kinases phosphorylate the same substrate. Through bioinformatics analysis we found that human cKSRs are frequent and involve >80% of all kinases and >24% of all substrates. We show that cKSRs occur over a wide range of stoichiometries harnessing converging kinases that are in many instances recruited from the same family subgroup and co-expressed. Experimentally, we demonstrate at the prototypical convergent CDK4/6 kinase pair how multiple inputs at the major tumor suppressor retinoblastoma protein (RB) can hamper in situ analysis of individual kinases. We hypothesized that overexpression of one kinase combined with a CDK4/6 inhibitor can dissect convergence. In breast cancer cells that express high levels of CDK4, we confirmed this hypothesis and developed a high throughput compatible assay that sensitively quantifies genetically modified CDK6 variants and small molecule or protein inhibitors. Collectively, our work provides deeper insights into the phosphorylation network through the identification and analysis of kinase convergence.
Leveraging the CSF proteome toward minimally-invasive diagnostics and biological characterization of brain malignancies
Authors: Mikolajewicz Nicholas , Khan Shahbaz , Trifoi Mara , Skakdoub Anna , Ignatchenko Vladmir , Mansouri Sheila , Zuccatto Jeffrey , Zacharia Brad E. , Glantz Michael , Zadeh Gelareh , Moffat Jason , Kislinger Thomas , Mansouri Alireza 
Published: June 2022

1AbstractBackgroundDiagnosis and prognostication of intra-axial brain tumors hinges on invasive brain sampling, which carries risk of morbidity. Minimally invasive sampling of proximal fluids, also known as liquid biopsy, can mitigate this risk.ObjectiveTo identify diagnostic and prognostic cerebrospinal fluid (CSF) proteomic signatures in glioblastoma (GBM), brain metastases (BM), and primary central nervous system lymphoma (CNSL).MethodsCSF samples were retrospectively retrieved from the Penn State Neuroscience Biorepository and profiled using shotgun proteomics. Proteomic signatures were identified using machine learning classifiers and survival analyses.ResultsUsing 30 µL CSF volumes, we recovered 755 unique proteins across 73 samples. Proteomic-based classifiers identified malignancy with area under the receiver operating characteristic (AUROC) of 0.94 and distinguished between tumor entities with AUROC ≥0.95. More clinically relevant triplex classifiers, comprised of just 3 proteins, distinguished between tumor entities with AUROC of 0.75-0.89. Novel biomarkers were identified, including GAP43, TFF3 and CACNA2D2, and characterized using single-cell RNA sequencing. Survival analyses validated previously implicated prognostic signatures, including blood brain barrier disruption.DiscussionReliable classification of intra-axial malignancies using low CSF volumes is feasible, allowing for longitudinal tumor surveillance. Based on emerging evidence, upfront implantation of CSF reservoirs in brain tumor patients warrants consideration.2Statement of SignificanceCurrent approaches to diagnosing brain tumors risk morbidity. The CSF may be an ideal liquid biopsy matrix for mitigating this risk. We report feasibility of high-throughput CSF proteomics on limited volumes from brain tumor patients with intraventricular reservoirs, demonstrate diagnostic and prognostic utility, and explore its applications in practice.
Environmental regulation of gene expression mediated by Long non-coding RNAs
Authors: Kang Jingliang , Chung Arthur , Suresh Sneha , Bonzi Lucrezia L. , Sourisse Jade M. , Ramirez Sandra , Romeo Daniele , Petit-Marty Natalia , Pegueroles Cinta , Schunter Celia 
Published: June 2022

ABSTRACTThe majority of the transcribed genome does not have coding potential but is composed of non-coding transcripts that are involved in transcriptional and post-transcriptional regulation of protein-coding genes. Regulation of gene expression is important in determining the response of organisms to changes in the environment, and therefore their persistence as population or species under global change. However, long non-coding RNAs (lncRNAs) are scarcely studied especially in non-model organisms due to the lack of a reliable pipeline for their accurate identification and annotation. Here, we present a pipeline which uses a combination of alignment-dependent and independent methods for the identification of conserved and species-specific lncRNAs from RNA-Seq data. Validation of this pipeline was performed using existing RNA-Seq data fromAcanthochromis polyacanthusbrain tissue, identifying a total of 4,728 lncRNAs across the genome, the majority of which (3,272) are intergenic. To investigate the possible implications of these intergenic lncRNAs (lincRNAs), we estimated the expression changes of lincRNAs and coding genes in response to ocean acidification. We found lincRNAs which neighbour or possibly trans-regulate differentially expressed coding genes related to pH regulation, neural signal transduction and ion transport, which are known to be important in the response to ocean acidification in fish. Overall, this pipeline enables the use of existing RNA sequencing data to reveal additional underlying molecular mechanisms involved in the response to environmental changes by integrating the study of lncRNAs with gene expression.
Estimating population split times and migration rates from historical effective population sizes
Authors: Shchur Vladimir , Brandt Débora Y. C. , Ilina Anna , Nielsen Rasmus 
Published: June 2022

AbstractThe estimation of effective population sizes (Ne) through time is of fundamental interest in population genetics, but the interpretation of Ne as the effective number of breeding individuals in the population is challenged by the effect of population structure. In fact, variation in Ne reported in many studies may be a consequence of changes in migration rates between populations rather than changes in actual population size. We address this long-standing problem here by constructing joint models of population size changes, migration, and divergence that can adjust temporal estimates of Ne and estimate the actual Ne of a local deme connected to another population through migration. We also develop a method for estimating divergence times and migration rates taking into account complex scenarios of changing population sizes. We apply the method to previously published data from humans, and show that, when taking migration and changes in Ne into account, the estimated divergence between the San and Dinka populations is approximately 108 kya, and not 255 kya as reported in a previous study. Using simulations, we demonstrate that the previously reported and surprisingly old estimates of divergence between San and Dinka is in fact caused by a quantifiable estimation bias due to changes in Ne through time.
Euler–Lagrange method for low-frequency metamaterials
Authors: Gong Zhi , Yang Shiyou , Guan Chongxi 
Published: June 2022

Purpose
The purpose of this paper is to develop a modeling method for the analysis of low-frequency metamaterials (MTMs) and their near-field applications.

Design/methodology/approach
The Euler–Lagrange method is introduced. An MTM is modeled as a multi-degree-of-freedom system without homogenization. The properties and the responses of the MTM in a near-field device are readily and rigorously studied through the motion equation derived from the Lagrange equations. The resonance frequencies and the corresponding resonance modes are solved from the characteristic equation.

Findings
The numerical results of the proposed method show good agreement with the experimental ones. A measurement of MTM-core coil resistance and inductance shows high accuracy of the proposed method.

Originality/value
The proposed Euler–Lagrange method provides a new study perspective and enables more flexible, rigorous and straightforward analysis of low-frequency MTMs in near-field applications. Consequently, the presented work greatly facilitates further explorations and studies on various novel MTM-based low-frequency near-field devices and systems.
Hidden multiwing chaotic attractors with multiple stable equilibrium points
Authors: Deng Quanli , Wang Chunhua , Wu Yazheng , Lin Hairong 
Published: June 2022

PurposeThe purpose of this paper is to construct a multiwing chaotic system that has hidden attractors with multiple stable equilibrium points. Because the multiwing hidden attractors chaotic systems are safer and have more dynamic behaviors, it is necessary to construct such a system to meet the needs of developing engineering.Design/methodology/approachBy introducing a multilevel pulse function into a three-dimensional chaotic system with two stable node–foci equilibrium points, a hidden multiwing attractor with multiple stable equilibrium points can be generated. The switching behavior of a hidden four-wing attractor is studied by phase portraits and time series. The dynamical properties of the multiwing attractor are analyzed via the Poincaré map, Lyapunov exponent spectrum and bifurcation diagram. Furthermore, the hardware experiment of the proposed four-wing hidden attractors was carried out.FindingsNot only unstable equilibrium points can produce multiwing attractors but stable node–foci equilibrium points can also produce multiwing attractors. And this system can obtain 2N+ 2-wing attractors as the stage pulse of the multilevel pulse function isN. Moreover, the hardware experiment matches the simulation results well.Originality/valueThis paper constructs a new multiwing chaotic system by enlarging the number of stable node–foci equilibrium points. In addition, it is a nonautonomous system that is more suitable for practical projects. And the hardware experiment is also given in this article which has not been seen before. So, this paper promotes the development of hidden multiwing chaotic attractors in nonautonomous systems and makes sense for applications.
Analysis of forced convective nanofluid flow through a wavy channel with linearly varying amplitude at the entrance
Authors: Kumar Ajit , Mehta Sumit Kumar , Pati Sukumar , Baranyi László 
Published: June 2022

Purpose
The purpose of this paper is to analyze the heat and momentum transfer for steady two-dimensional incompressible nanofluid flow through a wavy channel with linearly varying amplitude in the entrance region.

Design/methodology/approach
The mass, momentum and energy conservation equations for laminar flow of Cu-water nanofluids are computationally solved using the finite element method. A parametric study is carried out by varying the dimensionless length of the channel section with varying amplitude (EL), Reynolds number (Re) and nanoparticle volume fraction (Φ) in the ranges 0 ≤ EL ≤ 25.5, 105 ≤ Re ≤ 900 and 0 ≤ Φ ≤ 0.04.

Findings
A higher heat transfer rate is seen in the wavy channel compared to a plane channel beyond a critical value of Re (Recrit) whose value varies with EL; moreover, the overall heat transfer decreases with EL. The heat transfer rate increases with phi for all EL values investigated. The combined effects of the increase in the overall heat transfer and the associated pressure drop in the wavy channel compared to the parallel plate channel are presented as performance factor (PF) against EL. For the highest value of EL (= 25.5), PF monotonically decreases with Re. For smaller values of EL (= 5.5 and 11.5) and also for EL = 0, PF decreases with Re in the lower and the higher Re regimes, while it increases in the intermediate Re regime. In all cases, PF is higher for φ = 0.04 than for the base fluid. The sensitivity of the average Nusselt number to nanoparticle volume fraction follows a non-monotonic trend with the change in Re, φ and EL.

Practical implications
This study finds relevance in several applications such as solar collectors, heat exchangers and heat sinks.

Originality/value
To the best of the authors’ knowledge, the analysis of forced convection flow of nanofluid through a wavy channel with linearly varying amplitude is reported for the first time in the literature.
A systematic review on halal cosmetic consumption: application of theory method context – attributes decision outcome framework
Authors: Herjanto Halimin , Amin Muslim , Karmagatri Mulyani 
Published: June 2022

PurposeThis study aims to offer a holistic halal cosmetic consumption framework by describing the current knowledge about halal cosmetics and presenting new directions for future research.Design/methodology/approachThe theory, method and context–attributes, decision and outcome systematic review framework was used in this study. This study addresses the halal cosmetics literature published in the Scopus database: nonpredatory journals between 2010 and 2021.FindingsThis study found seven antecedent categories that affect four halal cosmetics consumption decisions. Those decisions led to three outcomes. In addition, behavioral theories were identified as the most frequent theory used to explain this phenomenon in personal and business settings.Originality/valueTo the best of the authors’ knowledge, this is the first systematic review of halal cosmetics consumption. This study explores the relevant theories, contexts, methods, antecedents and consumer decisions. Therefore, this study offers important insights into this phenomenon.
The impact of income gap on regional green economic growth – evidence from 283 prefecture-level cities in China
Authors: Hou Shiying , Song Liangrong , Dai Wanrui 
Published: June 2022

PurposeThis paper aims to research the relationship between income gap (IG) and green economic growth based on the perspective of economic inequality.Design/methodology/approachBased on the panel data of 283 prefecture-level cities in China from 2011 to 2020, this paper uses the super slack based model (Super-SBM) to measure the efficiency of regional green economic growth, and constructs a regression model of the IG and regional green economic growth.FindingsFirstly, the IG has an inhibitory effect on the growth of regional green economy (GE). Secondly, the relationship between the IG and regional green economic growth will be affected by the threshold value of income level. Thirdly, environmental regulation and government competition will increase the inhibitory effect of the IG.Originality/valueAccording to the characteristics of China's regional economy, the researchers construct an empirical model of the IG and green economic growth to study their relationship, the threshold effect of income level and the moderating effect of environmental regulation and local government competition. The research content, methods and conclusions of this paper provide new evidence for the sustainable growth of China's regional GE.
Establishing novel experimental operation teaching by a click-and-mortar environment
Authors: Wu Hsin-Te , Chung Kuo Cheng 
Published: June 2022

PurposeThis study aims to focus on the Artificial Intelligence of Things (AIoT) course. As AIoT has many theoretical theories and students usually have little interest in learning the protocols, the experiments can help stimulate their curiosity. Due to the environmental factor, the teaching requires assistive videos and Problem-Based Learning (PBL) to understand students' learning conditions.Design/methodology/approachThe experimental design generally follows the course theories going from easy to complex, and students can extend the acquired concepts to other project development, yet, without in-depth knowledge about the experiment, resulting in limited creativity.FindingsThe assessment analysis can reveal whether students have grown from the teaching. The final analysis at the end of the term can show learners' conditions; meanwhile, students can deliver their level of satisfaction. The click-and-mortar teaching environment provided in this research can improve learning setting and quality, solidifying learners' proficiency.Originality/valueThe research result has proved the feasibility of the proposed method. Apart from showing the experimental steps, the video also explains the corresponding theories, helping students reinforce experimental knowledge and boost learning willingness.
Aspects of contextual architecture regarding traditional/contemporary architecture, physical/cultural and place identity: a systematic literature review
Authors: Al-Hammadi Nessma A. Q. , Grchev Kokan 
Published: June 2022

PurposeAdopting Mapping Literature, the purpose of this study is to notice the tendency in defining contextualism through extrinsic aspects neglecting the intrinsic ones generating three theoretical gaps in understanding contextualism, especially in terms of (1) physical/cultural aspects (P/C); (2) traditional vs contemporary architecture (T/C); and (3) place identity (PI).Design/methodology/approachA directed systematic literature review (SLR) was conducted to investigate the Web of Science and Google Scholar engines for the related studies, resulting in 66 texts of book chapters, conferences, articles and practitioners’ texts. Using the PRISMA reporting method, the study presented the SLR procedure that narrowed the related studies to 66 texts of book chapters, conferences, articles and practitioners’ texts. Both consensus and debates in understanding the relation between contextualism and (T/C, P/C and PI) were re-visited (see Appendix).FindingsAccording to the findings, the studies tend to address contextualism through either extrinsic or intrinsic values. The undefined balance between extrinsic and intrinsic aspects in understanding and creating contextual architecture seems to be the common reason why the three theoretical gaps exist.Originality/valueThis paper did not only conduct an SLR investigation on the topic, which is limited in the field, but it also highlighted the need for further and constant discussions despite the previous one to improve the understanding of contextual architecture.