bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of Dynamic Binding of Replication Protein A to ssDNA
Authors: Mondal Anupam , Bhattacherjee Arnab
Published: March 2020

Replication protein A (RPA) serves as hub protein inside eukaryotic cells, where it coordinates crucial DNA metabolic processes and activates the DNA-damage response system. A characteristic feature of its action is to associate with ssDNA intermediates before handing over them to downstream proteins. The length of ssDNA intermediates differs for different pathways. This means RPA must have mechanisms for selective processing of ssDNA intermediates based on their length, the knowledge of which is fundamental to elucidate when and how DNA repair and replication processes are symphonized. By employing extensive molecular simulations, we investigated the mechanism of binding of RPA to ssDNA of different lengths. We show that the binding involves dynamic equilibrium with a stable intermediate, the population of which increases with the length of ssDNA. The vital underlying factors are decoded through collective variable principal component analysis. It suggests a differently orchestrated set of interactions that define the action of RPA based on the sizes of ssDNA intermediates. We further estimated the association kinetics and probed the diffusion mechanism of RPA to ssDNA. RPA diffuses on short ssDNA through progressive ‘bulge’ formation. With long ssDNA, we observed a conformational change in ssDNA coupled with its binding to RPA in a cooperative fashion. Our analysis explains how the ‘short-lived,’ long ssDNA intermediates are processed quickly in vivo. The study thus reveals the molecular basis of several recent experimental observations related to RPA binding to ssDNA and provides novel insights into the RPA functioning in DNA repair and replication.

Significance Statement

Despite ssDNA be the common intermediate to all pathways involving RPA, how does the latter function differently in the DNA processing events such as DNA repair, replication, and recombination just based on the length of ssDNA intermediates remains unknown. The major hindrance is the difficulty in capturing the transient interactions between the molecules. Even attempts to crystallize RPA complexes with 32nt and 62nt ssDNA have yielded a resolved structure of only 25nt ssDNA wrapped with RPA. Here, we used a state-of-the-art coarse-grained protein-ssDNA model to unravel the detailed mechanism of binding of RPA to ssDNA. Our study illustrates the molecular origin of variations in RPA action during various DNA processing events depending on the length of ssDNA intermediates.
A serological assay to detect SARS-CoV-2 seroconversion in humans
Authors: Amanat Fatima , Stadlbauer Daniel , Strohmeier Shirin , Nguyen Thi H.O. , Chromikova Veronika , McMahon Meagan , Jiang Kaijun , Arunkumar Guha Asthagiri , Jurczyszak Denise , Polanco Jose , Bermudez-Gonzalez Maria , Kleiner Giulio , Aydillo Teresa , Miorin Lisa , Fierer Daniel , Lugo Luz Amarilis , Kojic Erna Milunka , Stoever Jonathan , Liu Sean T. H. , Cunningham-Rundles Charlotte , Felgner Philip L. , Moran Thomas , Garcia-Sastre Adolfo , Caplivski Daniel , Cheng Allen , Kedzierska Katherine , Vapalahti Olli , Hepojoki Jussi M. , Simon Viviana , Krammer Florian
Published: March 2020

SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.
The impact of cell geometry and the cytoskeleton on the nucleo-cytoplasmic localisation of the SMYD3 methyltransferase suggests that the epigenetic machinery is mechanosensitive
Authors: Pereira David , Richert Alain , Medjkane Souhila , Hénon Sylvie , Weitzman Jonathan B
Published: March 2020

Mechanical cues from the cellular microenvironment are converted into biochemical signals controlling diverse cell behaviours, including growth and differentiation. But it is still unclear how mechanotransduction ultimately affects nuclear readouts, genome function and transcriptional programs. Key signaling pathways and transcription factors can be activated, and can relocalize to the nucleus, upon mechanosensing. Here, we tested the hypothesis that epigenetic regulators, such as methyltransferase enzymes, might also contribute to mechanotransduction. We found that the SMYD3 lysine methyltransferase is spatially redistributed dependent on cell geometry (cell shape and aspect ratio) in murine myoblasts. Specifically, elongated rectangles were less permissive than square shapes to SMYD3 nuclear accumulation, via reduced nuclear import. Notably, SMYD3 has both nuclear and cytoplasmic substrates. The distribution of SMYD3 in response to cell geometry correlated with cytoplasmic and nuclear lysine tri-methylation (Kme3) levels, but not Kme2. Moreover, drugs targeting cytoskeletal acto-myosin induced nuclear accumulation of Smyd3. We also observed that square vs rectangular geometry impacted the nuclear-cytoplasmic relocalisation of several mechano-sensitive proteins, notably YAP/TAZ proteins and the SETDB1 methyltransferase. Thus, mechanical cues from cellular geometric shapes are transduced by a combination of transcription factors and epigenetic regulators shuttling between the cell nucleus and cytoplasm.
Estimating Assembly Base Errors Using K-mer Abundance Difference (KAD) Between Short Reads and Genome Assembled Sequences
Authors: He Cheng , Lin Guifang , Wei Hairong , Tang Haibao , White Frank F , Valent Barbara , Liu Sanzhen
Published: March 2020

Genome sequences provide genomic maps with a single-base resolution for exploring genetic contents. Sequencing technologies, particularly long reads, have revolutionized genome assemblies for producing highly continuous genome sequences. However, current long-read sequencing technologies generate inaccurate reads that contain many errors. Some errors are retained in assembled sequences, which are typically not completely corrected by using either long reads or more accurate short reads. The issue commonly exists but few tools are dedicated for computing error rates or determining error locations. In this study, we developed a novel approach, referred to as K-mer Abundance Difference (KAD), to compare the inferred copy number of each k-mer indicated by short reads and the observed copy number in the assembly. Simple KAD metrics enable to classify k-mers into categories that reflect the quality of the assembly. Specifically, the KAD method can be used to identify base errors and estimate the overall error rate. In addition, sequence insertion and deletion as well as sequence redundancy can also be detected. Therefore, KAD is valuable for quality evaluation of genome assemblies and, potentially, provides a diagnostic tool to aid in precise error correction. KAD software has been developed to facilitate public uses.
Development and Use of miRNA-derived SSR Markers to Study Genetic Diversity, Population Structure and Characterization of Genotypes for Heat Tolerance Breeding in Bread Wheat (Triticum aestivumL.)
Authors: Tyagi Sandhya , Kumar Anuj , Gautam Tinku , Pandey Renu , Mir Reyazul Rouf
Published: March 2020

Wheat is one of the most important cereal crop in the world. Heat stress is an important abiotic stress limiting wheat production and productivity in the world including south-east Asia. The importance of miRNAs in gene expression under various biotic and abiotic stresses is well documented. Molecular markers, especially SSR markers, plays an important role for the success in molecular plant breeding programs. The discovery of SSRs from non-coding regions has been a challenging task. Therefore, development of novel miRNA-based SSRs from the conserved portions of the genome will prove useful for the study of genetic diversity of heat-responsive miRNA-genes in wheat. In the present study, efforts are made to mine SSR markers from 96 members of heat-responsive miRNA-genes of wheat followed by their validation using 37 contrasting (heat tolerance/susceptible) wheat genotypes. Among a set of 13 miRNA-SSRs used,7 SSRs were found polymorphic. Among these polymorphic SSR markers, three found to be very informative SSRs (HT-169j, HT-160a and HT-160b) and could largely discriminate heat tolerant genotypes from the heat susceptible ones. Further analysis based on Polymorphism Information Content (PIC) revealed that miRNA genes were more diverse in susceptible genotypes compared to tolerant genotypes. Ours is the first report that the genic/miRNA markers could be successfully used to study wheat diversity, population structure and characterization of trait specific germplasm. The important and useful miRNA-based SSRs, therefore, would serve as best markers in the marker-assisted breeding programs aimed at enhancing heat tolerance of Indian wheat.
Spatial analysis of American Eel (Anguilla rostrata), fish passage and land use in Chesapeake Bay tributaries
Authors: Walker Nicholas J. , Prasad V. , de Mutsert K. , Dolloff C.A. , Aguirre A.A.
Published: March 2020

Catadromous eels are found in more habitats than any other fish and are capable of inhabiting marine, brackish and freshwater environments. In this study we used the American Eel (Anguilla rostrata) as a bioindicator organism to create a novel method of using spatial analysis to study species conservation over landscape scales. We built a model of the subwatersheds of the Chesapeake Bay using a Digital Elevation Model (DEM) and overlaid eel density data (> 1 million eels sampled), dam density data and land use in ArcGIS. Dam construction in the study area peaked between 1955 and 1975, possibly as a result of flood control measures. Effects of land use were localized and most pronounced in areas around Baltimore, Maryland, Washington, D.C. and Richmond, Virginia, USA. Results indicate the Potomac and Rappahannock rivers appear to be areas of lesser concern while the upper James and York rivers are ideal for follow-up studies, since these area rank poorly in both eel density and barriers to fish passage. Because these rivers have high eel density downstream, the dams appear to be the limiting factor. Sampling methods have been inconsistent over time, making it is difficult to determine where eel densities are low vs. the area having had little sampling effort. This is partially resolved with catch per sampling event (CPSE), which appears to show a relationship between eels sampled and the number caught per sample. Potential strategies for improving watersheds include dam removal, fish passage and habitat restoration.
The Neuroprotective Beta Amyloid Hexapeptide Core Reverses Deficits in Synaptic Plasticity in the 5×FAD APP/PS1 Mouse Model
Authors: Forest Kelly H. , Taketa Ruth , Arora Komal , Todorovic Cedomir , Nichols Robert A.
Published: March 2020

Alzheimer’s disease (AD) is the most common cause of dementia in the aging population. Evidence implicates elevated soluble oligomeric Aβ as one of the primary triggers during the prodromic phase leading to AD, effected largely via hyperphosphorylation of the microtubule-associated protein tau. At low, physiological levels (pM-nM), however, oligomeric Aβ has been found to regulate synaptic plasticity as a neuromodulator. Through mutational analysis, we found a core hexapeptide sequence within the N-terminal domain of Aβ (N-Aβcore) accounting for its physiological activity, and subsequently found that the N-Aβcore peptide is neuroprotective. Here, we characterized the neuroprotective potential of the N-Aβcore against dysfunction of synaptic plasticity assessed inex vivohippocampal slices from 5×FAD APP/PS1 mice, specifically hippocampal long-term potentiation (LTP) and long-term depression (LTD). The N-Aβcore was shown to reverse impairment in synaptic plasticity in hippocampal slices from 5×FAD APP/PS1 model mice, both for LTP and LTD. The reversal by the N-Aβcore correlated with alleviation of downregulation of hippocampal AMPA-type glutamate receptors in preparations from 5×FAD mice. The action of the N-Aβcore depended upon a critical di-histidine sequence and involved the PI3 kinase pathway via mTOR. Together, the present findings indicate that the non-toxic N-Aβcore hexapeptide is not only neuroprotective at the cellular level but is able to reverse synaptic dysfunction in AD-like models, specifically alterations in synaptic plasticity.
Quantitative Properties of the Creation and Activation of a Cell-Intrinsic Engram
Authors: Gallistel C.R. , Johansson Fredrik , Jirenhed Dan-Anders , Rasmussen Anders , Ricci Matthew , Hesslow Germund
Published: March 2020

The conditional pause in the spontaneous firing of the cerebellar Purkinje, which determines the timing of the conditional eyeblink response, is mediated by a cell-intrinsic engram (Johansson, et al. 2014) that encodes the interstimulus interval. Our trial-by-trial analysis of the pause parameters reveals that it consists of a single unusually long interspike interval, whose onset and offset latencies are stochastically independent scalar functions of the interstimulus interval. The coefficients of variation are comparable to those observed in the timing of the overt conditional eyeblink. The onsets of the long interspike interval are step changes; there is no prior build-up of inhibition. A single spike volley in the parallel fiber input triggers the read-out of the engram into the long interspike interval; subsequent volleys have no effect on the pause. The high spontaneous firing rate on which the one-interval firing pause supervenes is markedly non-stationary (Fano factors >> 1).
pyComBat, a Python tool for batch effects correction in high-throughput molecular data using empirical Bayes methods
Authors: Behdenna Abdelkader , Colange Maximilien , Haziza Julien , Gema Aryo , Appé Guillaume , Azencott Chloé-Agathe , Nordor Akpéli
Published: March 2020

Background

Variability in datasets is not only the product of biological processes: they are also the product of technical biases. ComBat and ComBat-Seq are among the most widely used tools for correcting those technical biases, called batch effects, in, respectively, microarray and RNA-Seq expression data.

Results

In this technical note, we present a new Python implementation of ComBat and ComBat-Seq. While the mathematical framework is strictly the same, we show here that our implementations: (i) have similar results in terms of batch effects correction; (ii) are as fast or faster than the original implementations in R and; (iii) offer new tools for the bioinformatics community to participate in its development. pyComBat is implemented in the Python language and is distributed under GPL-3.0 (https://www.gnu.org/licenses/gpl-3.0.en.html) license as a module of the inmoose package. Source code is available athttps://github.com/epigenelabs/inmooseand Python package athttps://pypi.org/project/inmoose.

Conclusions

We present a new Python implementation of state-of-the-art tools ComBat and ComBat-Seq for the correction of batch effects in microarray and RNA-Seq data. This new implementation, based on the same mathematical frameworks as ComBat and ComBat-Seq, offers similar power for batch effect correction, at reduced computational cost.

Contact

akpeli@epigenelabs.com
A Robust Method for Collecting X-ray Diffraction Data from Protein Crystals across Physiological Temperatures
Authors: Doukov Tzanko , Herschlag Daniel , Yabukarski Filip
Published: March 2020

Traditional X-ray diffraction data collected at cryo-temperatures have delivered invaluable insights into the three-dimensional structures of proteins, providing the backbone of structure-function studies. While cryo-cooling mitigates radiation damage, cryo-temperatures can alter protein conformational ensembles and solvent structure. Further, conformational ensembles underlie protein function and energetics, and recent advances in room-temperature X-ray crystallography have delivered conformational heterogeneity information that is directly related to biological function. The next challenge is to develop a robust and broadly applicable method to collect single-crystal X-ray diffraction data at and above room temperatures and was addressed herein. This approach provides complete diffraction datasets with total collection times as short as ~5 sec from single protein crystals, dramatically increasing the amount of data that can be collected within allocated synchrotron beam time. Its applicability was demonstrated by collecting 1.09-1.54 Å resolution data over a temperature range of 293–363 K for proteinase K, thaumatin, and lysozyme crystals. Our analyses indicate that the diffraction data is of high-quality and do not suffer from excessive dehydration or damage.
Meta-analysis of diets used inDrosophilamicrobiome research and introduction of theDrosophilaDietary Composition Calculator (DDCC)
Authors: Lesperance Danielle N.A. , Broderick Nichole A.
Published: March 2020

While the term standard diet is commonly used in studies usingDrosophila melanogaster, more often than not these diets are anything but standard, making it difficult to contextualize results in the broader scope of the field. This is especially evident in microbiome studies, despite diet having a pivotal role in microbiome composition and resulting host-microbe interactions. Here, we performed a meta-analysis of diets used in fly microbiome research and provide a web-based tool for researchers to determine the nutritional content of diets of interest. Our goal is for these community resources to aid in contextualizing both past and future microbiome studies (with utility to other fields as well) to better understand how individual lab diets can contribute to observed phenotypes.
The landscape of longevity across phylogeny
Authors: Podolskiy Dmitriy I. , Avanesov Andrei , Tyshkovskiy Alexander , Porter Emily , Petrascheck Michael , Kaeberlein Matt , Gladyshev Vadim N.
Published: March 2020

Lifespan of model organisms can be extended by genetic, dietary and pharmacological interventions, but these effects may be negated by other factors. To understand robustness of longevity interventions within and across species, we analyzed age-dependent mortality of yeast, fruit flies, nematodes and mice subjected to thousands of genetic, pharmacological or dietary interventions, and applied the principles learned to other organisms. Across phylogeny, the accessible space of lifespan distribution functions, the “landscape of longevity”, has a distinct structure of a fiber bundle, with individual fibers given by Strehler-Mildvan degeneracy manifolds. Within species, most interventions perturb parameters of survival curves along particular degeneracy manifolds. Transitions across manifolds are difficult to achieve, but they may lead to robust lifespan-modulating effects. Analyses of intraspecific degeneracy manifolds revealed soft bounds on achievable longevity. For humans, this bound is ∼138 years.
TiTUS: Sampling and Summarizing Transmission Trees with Multi-strain Infections
Authors: Sashittal Palash , El-Kebir Mohammed
Published: March 2020

Motivation

The combination of genomic and epidemiological data hold the potential to enable accurate pathogen transmission history inference. However, the inference of outbreak transmission histories remains challenging due to various factors such as within-host pathogen diversity and multi-strain infections. Current computational methods ignore within-host diversity and/or multi-strain infections, often failing to accurately infer the transmission history. Thus, there is a need for efficient computational methods for transmission tree inference that accommodate the complexities of real data.

Results

We formulate the Direct Transmission Inference (DTI) problem for inferring transmission trees that support multi-strain infections given a timed phylogeny and additional epidemiological data. We establish hardness for the decision and counting version of the DTI problem. We introduce TiTUS, a method that uses SATISFIABILITY to almost uniformly sample from the space of transmission trees. We introduce criteria that prioritizes parsimonious transmission trees that we subsequently summarize using a novel consensus tree approach. We demonstrate TiTUS’s ability to accurately reconstruct transmission trees on simulated data as well as a documented HIV transmission chain.

Availability

https://github.com/elkebir-group/TiTUS

Contact

melkebir@illinois.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Rosetta Custom Score Functions Accurately Predict ΔΔG of Mutations at Protein-Protein Interfaces Using Machine Learning
Authors: Shringari Sumant , Giannakoulias Sam , Ferrie John J. , Petersson E. James
Published: March 2020

Protein-protein interfaces play essential roles in a variety of biological processes and many therapeutic molecules are targeted at these interfaces. However, accurate predictions of the effects of interfacial mutations to identify “hotspots” have remained elusive despite the myriad of modeling and machine learning methods tested. Here, for the first time, we demonstrate that nonlinear reweighting of energy terms from Rosetta, through the use of machine learning, exhibits improved predictability of ΔΔG values associated with interfacial mutations.
Nitrogen starvation and stationary phase lipophagy have distinct molecular mechanisms
Authors: Kumar Ravinder , Rahman Muhammad Arifur , Nazarko Taras Y.
Published: March 2020

In yeast, the selective autophagy of intracellular lipid droplets (LDs) or lipophagy can be induced by either nitrogen (N) starvation or carbon limitation (e.g. in the stationary (S) phase). We developed the yeast,Komagataella phaffii(formerlyPichia pastoris), as a new lipophagy model and compared the N-starvation and S-phase lipophagy in over 30 autophagy-related mutants using the Erg6-GFP processing assay. Surprisingly, two lipophagy pathways had hardly overlapping stringent molecular requirements. While the N-starvation lipophagy strictly depended on the core autophagic machinery (Atg1-Atg9, Atg18 and Vps15), vacuole fusion machinery (Vam7 and Ypt7) and vacuolar proteolysis (proteinases A and B), only Atg6 and proteinases A and B were essential for the S-phase lipophagy. The rest of the proteins were only partially required in the S-phase. Moreover, we isolated theprl1(for positive regulator of lipophagy 1) mutant affected in the S-phase lipophagy but not N-starvation lipophagy. Theprl1defect was at a stage of delivery of the LDs from the cytoplasm to the vacuole further supporting mechanistically different nature of the two lipophagy pathways. Taken together, our results suggest that N-starvation and S-phase lipophagy have distinct molecular mechanisms.
Technical Report: Targeted Proteomic Analysis Reveals Enrichment of Atypical Ubiquitin Chains in Contractile Murine Tissues
Authors: Heunis Tiaan , Lamoliatte Frederic , Marín-Rubio José Luis , Dannora Abeer , Trost Matthias
Published: March 2020

Ubiquitylation is an elaborate post-translational modification involved in all biological processes. Its pleotropic effect is driven by the ability to form complex polyubiquitin chain architectures that can influence biological functions. In this study, we optimised sample preparation and chromatographic separation of Ubiquitin peptides for Absolute Quantification by Parallel Reaction Monitoring (Ub-AQUA-PRM). Using this refined Ub-AQUA-PRM assay, we were able to quantify all ubiquitin chain types in 10-minute LC-MS/MS runs. We used this method to determine the ubiquitin chain-linkage composition in murine bone marrow-derived macrophages and different mouse tissues. We could show tissue-specific differences in ubiquitin levels in murine tissues, with polyubiquitin chain types contributing a small proportion to the total pool of ubiquitin. Interestingly, we observed enrichment of atypical (K33) ubiquitin chains in heart and muscle. Our approach enabled high-throughput screening of ubiquitin chain-linkage composition in different murine tissues and highlighted a possible role for atypical ubiquitylation in contractile tissues.
Label free fluorescence quantification of hydrolytic enzyme activity on native substrates reveal how lipase function depends on membrane curvature
Authors: Bohr Søren S.-R. , Thorlaksen Camilla , Kühnel Ronja Marie , Günther Pomorski Thomas , Hatzakis Nikos S.
Published: March 2020

Lipases are important hydrolytic enzymes used in a spectrum of technological applications, such as the pharmaceutical and detergent industry. Due to their versatile nature and ability to accept a broad range of substrates they have been extensively used for biotechnological and industrial applications. Current assays to measure lipase activity primarily rely on low sensitivity measurement of pH variations or visible changes on material properties, like hydration, and often require high amount of proteins. Fluorescent readouts on the other hand offer high contrast and even single molecule sensitivity, albeit they are reliant on fluorogenic substrates that structurally resemble the native ones. Here we present a method that combines the highly sensitive readout of fluorescent techniques while reporting enzymatic lipase function on native substrates. The method relies on embedding the environmentally sensitive fluorescent dye pHrodo and native substrates into the bilayer of liposomes. The charged products of the enzymatic hydrolysis alter the local membrane environment and thus the fluorescence intensity of pHrodo. The fluorescence can be accurately quantified and directly assigned to product formation and thus enzymatic activity. We illustrated the capacity of the assay to report function of diverse lipases and phospholipases both in a microplate setup and at the single particle level on individual nanoscale liposomes using Total Internal Reflection Fluorescence (TIRF). The parallelized sensitive readout of microscopy combined with the inherent polydispersity in sizes of liposomes allowed us to screen the effect of membrane curvature on lipase function and identify how mutations in the lid region control the membrane curvature dependent activity. We anticipate this methodology to be applicable for sensitive activity readouts for a spectrum of enzymes where the product of enzymatic reaction is charged.
Time course regulatory analysis based on paired expression and chromatin accessibility data
Authors: Duren Zhana , Chen Xi , Xin Jingxue , Wang Yong , Wong Wing Hung
Published: March 2020

A time course experiment is a widely used design in the study of cellular processes such as differentiation or response to stimuli. In this paper, we propose time course regulatory analysis (TimeReg) as a method for the analysis of gene regulatory networks based on paired gene expression and chromatin accessibility data from a time course. TimeReg can be used to prioritize regulatory elements, to extract core regulatory modules at each time point, to identify key regulators driving changes of the cellular state, and to causally connect the modules across different time points. We applied the method to analyze paired chromatin accessibility and gene expression data from a retinoic acid (RA)–induced mouse embryonic stem cells (mESCs) differentiation experiment. The analysis identified 57,048 novel regulatory elements regulating cerebellar development, synapse assembly, and hindbrain morphogenesis, which substantially extended our knowledge of cis-regulatory elements during differentiation. Using single-cell RNA-seq data, we showed that the core regulatory modules can reflect the properties of different subpopulations of cells. Finally, the driver regulators are shown to be important in clarifying the relations between modules across adjacent time points. As a second example, our method on Ascl1-induced direct reprogramming from fibroblast to neuron time course data identified Id1/2 as driver regulators of early stage of reprogramming.
An assessment into mechanical properties and microstructural behavior of TIG welded Ti-6Al-4V titanium alloy
Authors: Dewangan Saurabh , Mohapatra Suraj Kumar , Sharma Abhishek
Published: March 2020

Purpose

Titanium (Ti) alloys are in high demand in manufacturing industries all over the world. The property like high strength to weight ratio makes Ti alloys highly recommended for aerospace industries. Ti alloys possess good weldability, and therefore, they were extensively investigated with regard to strength and metallurgical properties of welded joint. This study aims to deal with the analysis of strength and microstructural changes in Ti-6Al-4V (Grade 5) alloy after tungsten inert gas (TIG) welding.

Design/methodology/approach

Two pair of Ti alloy plates were welded in two different voltages, i.e. 24 and 28 V, with keeping the current constant, i.e. 80 A It was a random selection of current and voltage values to check the performance of welded material. Both the welded plates were undergone through some mechanical property analysis like impact test, tensile test and hardness test. In addition, the microstructure of the welded joints was also analyzed.

Findings

It was found that hardness and tensile properties gets improved with an increment in voltage, but this effect was reverse for impact toughness. A good corroboration between microstructure and mechanical properties, such as tensile strength, hardness and toughness, was reported in this work. Heat distribution in both the welded plates was simulated through ANSYS software to check the temperature contour in the plates.

Originality/value

A good corroboration between microstructure and mechanical properties, such as tensile strength, hardness and toughness, was reported in this study.
Health, well-being and education
Authors: Dadaczynski Kevin , Jensen Bjarne Bruun , Viig Nina Grieg , Sormunen Marjorita , von Seelen Jesper , Kuchma Vladislav , Vilaça Teresa
Published: March 2020

Purpose

The purpose of this paper is to introduce the official statement of the Fifth European Conference on Health-Promoting Schools.

Design/methodology/approach

The Fifth European Conference on Health-Promoting Schools was held on 20–22 November 2019 in Moscow, Russian Federation, with over 450 participants from 40 countries. A writing group was established to prepare a draft version of the statement before the conference. On the basis of an online and offline feedback process, the opinions of the participants were collected during the conference and included in the finalisation of the statement.

Findings

The final conference statement comprises six thematic categories (values and principles; environment, climate and health; schools as part of the wider community; non-communicable diseases (NCDs); evidence base; and digital media), with a total of 23 recommendations and calls for action.

Originality/value

The recommendations and calls for action reflect current challenges for Health Promoting Schools in Europe. They are addressed to all actors in governmental, non-governmental and other organisations at international, national and regional levels involved in health promotion in schools and are to be applied for the further development of the concept.
The path of teachers' learning through lesson and learning studies
Authors: Wood Keith
Published: March 2020

Purpose

The purpose of this article is to discern and discuss dimensions of variation opened by the articles in the issue 9(2) of the International Journal of Lesson and Learning Studies (IJLLS).

Design/methodology/approach

The approach draws on the path of teachers learning through lesson and learning studies presented as a pattern of variation forming a temporal sequence.

Findings

Attention is drawn to the importance of being explicit about the theory of learning informing lesson and learning studies and how its implementation leads to teacher learning.

Originality/value

The depiction of the path of learning through lesson and learning studies is original.
Theoretical explanation, understanding and prediction in management studies
Authors: Styhre Alexander
Published: March 2020

Purpose

The purpose of this paper is to question whether the management studies is rigorous and/or relevant is a recurrent debate in the discipline. There is reason to believe that this dichotomy is simplistic as relevance is a consequence of rigor (defined in a variety of ways in the literature), whereas the epistemic value of rigor must per se be examined in more detail.

Design/methodology/approach

Drawing on the study of the analytical philosophy of Donald Davidson, rigor is here conceptualized as the capacity to examine how intersubjective meaning is constituted on the basis of the semantics of the everyday language.

Findings

In Davidson’s pragmatist view, individual beliefs are established through communication, and beliefs generate preferences and “pro-attitudes” that result in social action. Using Ian Hacking’s term undoing as a critique of a proposition or idea as being no contender for truth (or some other quality) at all, the paper questions the proposition that scientific rigor can be operationalized as the use of data collection and analysis methods developed in other and more authoritative disciplines, e.g. economics. On the contrary, to make accurate descriptions of beliefs, preferences and actions on the basis of the use of everyday language is the mark of scientific rigor in management studies.

Originality/value

The paper addresses the question of how rigorous research in management studies is essentially a matter of explanation, and that explanation, in turn, demands a more elaborate theory of action. The paper also introduces the work of Donald Davidson as an important figure when theorizing action.
Deviation from the direction of motion across gaits in a hexapodal robot
Authors: Niu Zijie , Zhan Aiwen , Cui Yongjie
Published: March 2020

Purpose

The purpose of this study is to test a chassis robot on rugged road cargo handling.

Design/methodology/approach

Attitude solution of D-H series robot gyroscope speed and acceleration sensor.

Findings

In identical experimental environments, hexapodal robots experience smaller deviations when using a four-footed propulsive gait from a typical three-footed gait for forward motion; for the same distance but at different speeds, the deviation basically keeps itself within the same range when the robot advances forward with four-foot propulsive gait; because the foot slide in the three-footed gait sometimes experiences frictions, the robot exhibits a large gap in directional deviations in different courses during motion; for motion using a four-footed propulsive gait, there are minor directional deviations of hexapodal robots resulting from experimental errors, which can be reduced through optimizing mechanical structures.

Originality/value

Planning different gaits can solve problems existing in some typical gaits. This article has put forward a gait planning method for hexapodal robots moving forward with diverse gaits as a redundant multifreedom structure. Subsequent research can combine a multiparallel-legged structure to analyze kinematics, optimize the robot’s mechanical structure and carry out in-depth research of hexapod robot gaits.
Medical treatment and best interests: judicial interpretation of values, wishes and beliefs under the Mental Capacity Act 2005
Authors: O'Sullivan Owen P.
Published: March 2020

Purpose

The prominence of the best interests principle in the Mental Capacity Act 2005 represented an important transition to a more resolutely patient-centred model regarding decision-making for incapable adults (“P”). This paper aims to examine the courts’ consideration of P’s values, wishes and beliefs in the context of medical treatment, reflect on whether this has resulted in a wide interpretation of the best interests standard and consider how this impacts clinical decision makers.

Design/methodology/approach

A particular focus will be on case law from the Court of Protection of England and Wales and the Supreme Court of the UK. Cases have been selected for discussion on the basis of the significance of their judgements for the field, the range of issues they illustrate and the extent of commentary and attention they have received in the literature. They are presented as a narrative review and are non-exhaustive.

Findings

With respect to values, wishes and beliefs, the best interests standard’s interpretation in the courts has been widely varied. Opposing tensions and thematic conflicts have emerged from this case law and were analysed from the perspective of the clinical decision maker.

Originality/value

This review illustrates the complexity and gravity of decisions of the clinical decision makers and the courts have considered in the context of best interests determinations for incapacitated adults undergoing medical treatment. Subsequent to the first such case before the Supreme Court of the UK, emerging case law trends relating to capacity legislation are considered.
How can gamification contribute to achieve SDGs?
Authors: Souza Viviane Silva , Marques Susana Regina Bacelar de Vasconcelos , Veríssimo Medéia
Published: March 2020

Purpose

Ecogamification can make a positive impact on Tourism. With this in mind, the present study aims to examine specific stakeholders – those positioned at the upstream side of gamification process – and their perspectives concerning not only the benefits, but also the challenges of (eco)gamification.

Design/methodology/approach

The study follows a qualitative-exploratory approach and bases its results on the analysis of 10 in-depth interviews conducted with buyers and providers from the emerging Portuguese tourism and tech markets.

Findings

Results shed light on key benefits of ecogamification, including its potential to promote “green” behaviour, transmit complex information through entertainment, reward users for good practices, improve engagement and help avoiding overtourism. Simultaneously, there are important challenges to overcome, including the lack of investment, resistance to new technologies, low eco-consciousness of tourists and distraction from issues that matter. Further, findings show that ecogamification takes on different and specific roles for buyers and providers.

Research limitations/implications

The research limitations are mainly related to the sample size.

Practical implications

An effective ecogamification process depends on the integration of the supply and demand sides and, at the same time, on the responsibility of different stakeholders (providers, buyers, players) across the value chain, through a broad logic of B2B2C.

Originality/value

This study contributes towards a better understanding of ecogamification in tourism, through the eyes of buyers and providers and also provides insights regarding the role of these specific stakeholders and the relationship between them.
Access services statistics: showing our story through LibInsight
Authors: Sewell Bethany Badgett , Cowell Amanda
Published: March 2020

Purpose

The purpose of this paper is to evaluate the Springshare tool LibInsight, and describe the ways it was implemented at the R. Barbara Gitenstein Library at The College of New Jersey.

Design/methodology/approach

Going beyond traditional data collection, LibInsight allows the library to blend and analyze library data in a single dashboard. It enables decision-makers to see analytics presented visually, identify new patterns and quickly address problems or opportunities. LibInsight can visualize, evaluate and assess library services and collections and compare them both internally and against industry standards.

Findings

Historical data for data sets ranging from gate counts and circulation were uploaded into LibInsight. In addition, custom data sets were created and new data, such as patron activity at the circulation desk, was collected.

Originality/value

This is a review of the product, LibInsight, and data sets kept in access services.
Convective instability analysis of couple-stress dielectric fluid saturated anisotropic porous medium with radiation effect
Authors: Myson Shruthy , Nagouda Smita Saklesh
Published: March 2020

Purpose

The effects of anisotropy and radiation cannot be considered negligible while investigating the stability of the fluid in convection. Hence, the purpose of this paper is to analyze how these effects could affect the system while considering a couple-stress dielectric fluid. Therefore, the study establishes the effect of thermal radiation in a couple-stress dielectric fluid with an anisotropic porous medium using Goody's approach (Goody, 1956).

Design/methodology/approach

To analyze the effect of radiation on the onset of convection, the Milne–Eddington approximation is employed to convert radiative heat flux to thermal heat flux. The equations are further developed to approximate for transparent and opaque medium. Stability of the quiescent state within the framework of linear theory is performed. The principle of exchange of stabilities is shown to be valid by means of single-term Galerkin method. Large values of conduction–radiation and absorptivity parameters are avoided as fluid is considered as liquid rather than gas.

Findings

The radiative heat transfer effect on a couple-stress dielectric fluid saturated anisotropic porous medium is examined in terms of Milne–Eddington approximation. The effect of couple-stress, dielectric, anisotropy and radiation parameters are analyzed graphically for both transparent and opaque medium. It is observed that the conduction–radiation parameter stabilizes the system; in addition, the critical Darcy–Rayleigh number also shows a stabilizing effect in the absence of couple-stress, dielectric and anisotropy parameters, for both transparent and opaque medium. Furthermore, the absorptivity parameter stabilizes the system in the transparent medium, whereas it exhibits a dual effect in the case of an opaque medium. It was also found that an increase in thermal and mechanical anisotropy parameters shows an increase in the cell size, whereas the increase in Darcy–Roberts number and conduction–radiation parameter decreases the cell size. The validity of principle of exchange of stability is performed and concluded that marginal stability is the preferred mode than oscillatory.

Originality/value

The effects of anisotropy and radiation on Rayleigh–Bénard convection by considering a couple-stress dielectric fluid has been analyzed for the first time.
Introduction of new surface geometry to join Ti-6Al-4V and SS304L by friction welding
Authors: Balasubramanian M. , Kumar R.
Published: March 2020

Purpose

In friction welding of dissimilar joint method, few material compositions are not possible to weld effectively. For better dissimilar metal joining in friction welding, the interlayer techniques are used by the third metal to increase the diffusion for suitable metal bonding. The interlayer metals are popularly held by coating, foils, sheet and solid rod form. The coating method needs more care for surface preparation with special coating equipment with high workmanship. In case of foil as intermediate metal, more care is neededfor holding between the metal; most of the time this technique has the possibility of failure by peeling off from the contact surface during high speed rotation with pressure during friction generation.

Design/methodology/approach

In this investigation, a copper coin was machined to a suitable size (transition fit) to suit the recess inside the SS rod. The mating surfaces of Cu coin, SS rod and Ti alloy were machined, polished to mirror finish and handled in friction welding machine. The purpose of the transition fit between the coin and SS rod is for holding the same intact before the beginning of the process.

Findings

Successful joint was achieved with good joint strength at less time. Empirical models were established to fin out the joint strength at any given parameter within the range of investigation

Research limitations/implications

The models developed can be used only within the range of investigation considered for experimentation.

Practical implications

The paper includes implications for the development of a method of joining any dissimilar joints

Originality/value

In this investigation, a copper coin was machined to a suitable size (transition fit) to suit the recess inside the SS rod. The mating surfaces of Cu coin, SS rod and Ti alloy were machined, polished to mirror finish and handled in friction welding machine. The purpose of the transition fit between the coin and SS rod is for holding the same intact before the beginning of the process.
Vegetable and fruit consumption and its association with bone turnover biomarkers in older adults
Authors: Djafari Farhang , Shahinfar Hossein , Safabakhsh Maryam , Shab-Bidar Sakineh
Published: March 2020

Purpose

Fruits and vegetables (FVs) are a good source of substances that contributed to bone health. However, the relation of FVs consumption with inflammation and bone biomarkers is inconsistent. Thus, this paper aims to assess the association of FVs intake with inflammation and bone biomarkers in older adults.

Design/methodology/approach

This cross-sectional study was performed on 178 older adults in Tehran, with a mean age of 67.04. Biochemical measurements including serum osteocalcin, high sensitivity c-reactive protein, 25-hydroxyvitamin D 25(OH) D, parathormone and urine terminal telopeptide of Type I collagen (u-CTx) was done. The intake of FVs was calculated using a validated quantitative food frequency questionnaire.

Findings

Pearson correlation coefficients showed a positive relation between serum osteocalcin and total vegetables (r = 0.167, p = 0.026), juices group (r = 0.155, p = 0.035), starchy vegetables (r = 0.205, p = 0.006) and other vegetable group (r = 0.161, p = 0.032) even after controlling of potential confounders. Analysis of covariance showed that total vegetable were significantly associated with serum osteocalcin (p = 0.041) and PTH levels (p = 0.028). Additionally, no evidence of a significant relationship between total fruit intake and test variables was observed. However, subgroup analyses demonstrated a significant association between citrus fruits and serum 25(OH) D (p = 0.017). A significant relation between starchy vegetable and urine CTx-I was reported (p = 0.016). Moreover, other vegetable subgroup was strongly associated with serum osteocalcin (p = 0.003).

Originality/value

The results of this paper may provide insight for clinical interventions and also important to make policy for prevention or easing bone disorders and general inflammation related to fruit and vegetable intake.