bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving Reversible Ligand-Protein Unbinding with Deep Learning and Molecular Dynamics through RAVE
Authors: Lamim Ribeiro João Marcelo , Tiwary Pratyush
Published: August 2018

In this work we demonstrate how to leverage our recent iterative deep learning–all atom molecular dynamics (MD) technique “Reweighted autoencoded variational Bayes for enhanced sampling (RAVE)” (Ribeiro, Bravo, Wang, Tiwary, J. Chem. Phys. 149, 072301 (2018)) for sampling protein-ligand unbinding mechanisms and calculating absolute binding affinities when plagued with difficult to sample rare events. RAVE iterates between rounds of MD and deep learning, and unlike other enhanced sampling methods, it stands out in simultaneously learning both a low-dimensional physically interpretable reaction coordinate (RC) and associated free energy. Here, we introduce a simple but powerful extension to RAVE which allows learning a position-dependent RC expressed as a superposition of piecewise linear RCs valid in different metastable states. With this approach, we retain the original physical interpretability of a RAVE-derived RC while making it applicable to a wider range of complex systems. We demonstrate how in its multi-dimensional form introduced here, RAVE can efficiently simulate the unbinding of the tightly bound benzene-lysozyme (L99A variant) complex, in all atom-precision and with minimal use of human intuition except for the choice of a larger dictionary of order parameters. These simulations had a 100 % success rate, and took between 3–50 nanoseconds for a process that takes on an average close to few hundred milliseconds, thereby reflecting a seven order of magnitude acceleration relative to straightforward MD. Furthermore, without any time-dependent biasing, the trajectories display clear back–and– forth movement between various metastable intermediates, demonstrating the reliability of the RC and its probability distribution learnt in RAVE. Our binding free energy is in good agreement with other reported simulation results. We thus believe that RAVE, especially in its multi-dimensional variant introduced here, will be a useful tool for simulating the dissociation process of practical biophysical systems with rare events in an automated manner with minimal use of human intuition.
Engineered transfer RNAs for suppression of premature termination codons
Authors: Lueck John D. , Yoon Jae Seok , Perales-Puchalt Alfredo , Mackey Adam L. , Infield Daniel T. , Behlke Mark A. , Pope Marshall R. , Weiner David B. , Skach William R. , McCray Paul B. , Ahern Christopher A.
Published: August 2018

Premature termination codons (PTCs) are responsible for 10-15% of all inherited disease. PTC suppression during translation offers a promising approach to treat a variety of genetic disorders, yet small molecules that promote PTC read-through have yielded mixed performance in clinical trials. We present a high-throughput, cell-based assay to identify anticodon engineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In total, we identified ACE-tRNA with a high degree of suppression activity targeting the most common human disease-causing nonsense codons. Genome-wide transcriptome ribosome profiling of cells expressing ACE-tRNA at levels which repair PTC indicate that there are limited interactions with translation termination codons. These ACE-tRNAs display high suppression potency in mammalian cells, Xenopus oocytes and mice in vivo, producing PTC repair in multiple genes, including disease causing mutations within the cystic fibrosis transmembrane conductance regulator (CFTR).
Evidence for the Modulation of the Immune Response in Peripheral Blood Mononuclear Cells after Stimulation with a High Molecular Weight β-glucan Isolated fromLactobacillus fermentumLf2
Authors: Vitlic Ana , Sadiq Sohaib , Ahmed Hafiz I. , Ale Elisa C. , Binetti Ana G. , Collett Andrew , Humpreys Paul N. , Laws Andrew P.
Published: August 2018

Lactobacillus fermentumLf 2 produces large amounts of exopolysaccharides under optimized conditions (∼2 g/L, EPS) which have been shown to possess immunomodulatory activity. In this study, the crude EPS was fractionated to give a high molecular weight (HMw) homoglycan and a mixture of medium molecular weight heteroglycans. The HMw EPS was isolated and identified as a β-glucan.

Peripheral blood mononuclear cells (PBMC) were pre-treated with purified polysaccharide to determine if the HMw β-glucan is responsible for the immunomodulatory activity. Cells were also stimulated with either lipopolysaccharide (LPS) or phytohemagglutinin (PHA) and their effects, both with and without β-glucan pre-treatment, compared.

Exposure of the cells to β-glucan increased their metabolic activity and whilst a small but statistically significant drop in CD14 expression was observed at Day 1, the levels were significantly elevated at Day 2. High levels of CD14 expression were observed in cells initially exposed to the β-glucan and subsequently stimulated with either LPS or PHA. In contrast, reduced levels of TLR-2 expression were observed for cells initially exposed to the β-glucan and subsequently stimulated with LPS.

TNF-α levels were elevated in β-glucan treated cells (Day1) with the levels dropping back once the β-glucan had been removed (Day 2). The stimulants LPS and PHA both induced significant rises in TNF-α levels, however, this induction was completely (LPS) or partially blocked (PHA) in β-glucan pre-treated cells.

The results indicate a role for the bacterial β-glucan in modulating the immune response following exposure to agonists such as bacterial LPS.
Multichannel Silicon Probes for Awake Hippocampal Recordings in Large Animals
Authors: Ulyanova Alexandra V. , Cottone Carlo , Adam Christopher D. , Gagnon Kimberly G. , Cullen D. Kacy , Holtzmann Tahl , Jameison Brian , Koch Paul F. , Chen H. Isaac , Johnson Victoria E. , Wolf John A.
Published: August 2018

Decoding laminar information across deep brain structures and cortical regions is necessary in order to understand the spatiotemporal ensembles that represent cognition and memory. Large animal models are essential for translational research due to their gyrencephalic neuroanatomy and significant white matter composition. One of the major obstacles to applying the approaches currently utilized in lower order animals are technical limitations in silicon probes, specifically a lack of long-length probes with appropriate stiffness to penetrate to deeper structures with minimal damage to the neural interface. We tested various solutions and designs of multichannel silicon probes developed for large animal electrophysiology by recording neurophysiological signals from deep laminar structures in an acute preparation and in chronically implanted awake behaving Yucatan pigs. Electrophysiological parameters of single units and local field potentials were analyzed to evaluate performance over time of given silicon probes in chronic implantations. The cross-sectional area of silicon probes was found to be a crucial determinant of silicon probes’ single unit performance over time, potentially due to reduction of damage to the neural interface. EDGE-style probes had the highest yields during intra-hippocampal recordings in pigs, making them the most suitable for chronic implantations and awake behavioral experimentation. Novel CAMB 64-channel EDGE-style probes with linear and poly-2 site arrangement tested acutely had optimal single unit separation and a denser sampling of the laminar structure, identifying them as potential candidates for chronic implantations with less cortical damage above the active portion of the probe. This study provides an analysis of multichannel silicon probes designed for large animal laminar electrophysiology of deep brain structures, and suggests that current designs are reaching the physical thresholds necessary for long-term (~ 1 month) recordings from laminar deep structures with single-unit resolution.
Sequencing of the MHC region defines HLA-DQA1 as the major independent risk for anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis in Han population
Authors: Guo Jianping , Zhang Tao , Cao Hongzhi , Li Xiaowei , Liang Hao , Liu Mengru , Zou Yundong , Zhang Yuanwei , Sun Xiaolin , Hu Fanlei , Du Yan , Mo Xiaodong , Liu Xu , Yang Yue , Yang Huanjie , Wu Xinyu , Zhang Xuewu , Jia Huijue , Jiang Hui , Hou Yong , Liu Xin , Su Yin , Zhang Mingrong , Yang Huanming , Wang Jian , Sun Liangdan , Liu Liang , Padyukov Leonid , Lai Luhua , Yamamoto Kazuhiko , Zhang Xuejun , Klareskog Lars , Xu Xun , Li Zhanguo
Published: August 2018

The strong genetic contribution of the major histocompatibility complex (MHC) to rheumatoid arthritis (RA) susceptibility has been generally attributed to HLA-DRB1. However, due to the high linkage disequilibrium in the MHC region, it is difficult to define the ‘real’ or/and additional independent genetic risks using the conventional HLA genotyping or chip-based microarray technology. By the capture sequencing of entire MHC region for discovery and HLA-typing for validation in 2,773 subjects of Han ancestry, we identified HLA-DQα1:160D as the strongest independent genetic risk for anti-citrullinated protein antibodies (ACPA)-positive RA in Han population (P = 6.16 × 10−36, OR=2.29). Further stepwise conditional analysis revealed that DRβ1:37N has an independent protective effect on ACPA–positive RA (P = 5.81 × 10−16, OR=0.49). The DQα1:160 coding allele DQA1*0303 displayed high impact on joint radiographic severity, especially in patients with early disease and smoking (P = 3.02 × 10−5). Interaction analysis by comparative molecular modeling revealed that the negative charge of DQα1:160D stabilizes the dimer of dimers, leading to an increased T cell activation. The electrostatic potential surface analysis indicated that the negative charged DRβ1:37N encoding alleles could bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.

In this study, we provide the first evidence that HLA-DQA1, instead of HLA-DRB1, is the strongest and independent genetic risk for ACPA-positive RA in Chinese Han population. Our study also illustrates the value of MHC deep sequencing for fine mapping disease risk variants in the MHC region.
Visual intensity ratio modulates operant learning responses in larval zebrafish
Authors: Yang Wenbin , Meng Yutong , Li Danyang , Wen Quan
Published: August 2018

Larval zebrafish is a promising vertebrate model for understanding neural mechanisms underlying learning and memory. Here, we report on a high-throughput operant learning system for zebrafish larvae and demonstrate that lower visual intensity ratio of the conditioned stimulus to the background can enhance learning ability, highlighted by several behavioral metrics. We further characterize the learning curves as well as memory extinction for each conditioned pattern. Finally, we show how this learning process developed from 7 days old to 10 days old zebrafish.

Highlights

Conditioned visual patterns with lower intensity ratio to the background elicited stronger operant learning responses

Memory extinction was modulated by the visual intensity ratio of the conditioned stimulus to the background

A high-throughput automated system for acquiring and analyzing behavioral data
Differential amplicons for the evaluation of RNA integrity extracted from complex environmental samples
Authors: Cholet Fabien , Ijaz Umer Z. , Smith Cindy J.
Published: August 2018

Background

Reliability and reproducibility of transcriptomics-based studies are highly dependent on the integrity of RNA. Microfluidics-based techniques based on ribosomal RNA such as the RNA Integrity Number (RIN) are currently the only approaches to evaluate RNA integrity. However, it is not known if ribosomal RNA reflects the integrity of the meaningful part of the sample, the mRNA. Here we test this assumption and present a new integrity index, the Ratio amplicon, Ramp, to monitor mRNA integrity based on the differential amplification of long to short RT-Q-PCR amplicons of the glutamine synthetase A (glnA) transcript.

Results

We successfully designed and tested two Rampindexes targetingglnAtranscripts. We showed in a suite of experimental degradations of RNA extracted from sediment that while the RIN in general did reflect the degradation status of the RNA well the Rampmapped mRNA degradation better as reflected by changes in Reverse Transcriptase Quantitative PCR (RT-Q-PCR) results. Furthermore, we examined the effect of degradation on transcript community structure by amplicon sequencing of the16S rRNA, amoAandglnAtranscript which was successful even form the highly-degraded samples. While RNA degradation changed the community structure of the mRNA profiles, no changes were observed between successively degraded 16S rRNA transcripts profiles.

Conclusion

As demonstrated, transcripts can be quantified and sequenced even from highly degraded samples. Therefore, we strongly recommend that a quality check of RNA is conducted to ensure validity of results. For this both the RIN and Rampare useful, with the Rampbetter evaluating mRNA integrity in this study.
Modulation of the spontaneous hemodynamic response function across levels of consciousness
Authors: Wu Guo-Rong , Perri Carol Di , Charland-Verville Vanessa , Martial Charlotte , Laureys Steven , Marinazzo Daniele
Published: August 2018

Functional imaging research has already contributed with several results to the study of neural correlates of consciousness. Apart from task-related activation derived in fMRI, PET based glucose metabolism rate or cerebral blood flow account for a considerable proportion of the study of brain activity under different levels of consciousness. Resting state functional connectivity MRI is playing a crucial role to explore the consciousness related functional integration, successfully complementing PET, another widely used neuroimaging technique. Here, spontaneous hemodynamic response is introduced to characterize resting state brain activity giving information on the local metabolism (neurovascular coupling), and useful to improve the time-resolved activity and connectivity measures based on BOLD fMRI. This voxel-wise measure is then used to investigate the loss of consciousness under Propofol anesthesia and unresponsive wakefulness syndrome. The dysfunction of hemodynamic response in precuneus and posterior cingulate is found to be a common principle underlying loss of consciousness in both conditions. The thalamus appears to be less obviously modulated by Propofol, compared with frontoparietal regions. However, a significant increase in spontaneous thalamic hemodynamic response was found in patients in unresponsive wakefulness syndrome compared with healthy control. Our results ultimately show that anesthesia- or pathology-induced neurovascular coupling could be tracked by modulated spontaneous hemodynamic response derived from resting state fMRI.
Polarity signaling ensures epidermal homeostasis by coupling cellular mechanics and genomic integrity
Authors: Gomes Martim Dias , Letzian Soriba , Saynisch Michael , Iden Sandra
Published: August 2018

Epithelial homeostasis requires balanced progenitor cell proliferation and differentiation, whereas disrupting this equilibrium fosters degeneration or cancer. Here we studied how cell polarity signaling orchestrates epidermal self-renewal and differentiation. Using genetic ablation, quantitative imaging, mechanochemical reconstitution and atomic force microscopy, we find that mammalian Par3 couples genome integrity and epidermal fate through shaping keratinocyte mechanics, rather than mitotic spindle orientation. Par3 inactivation impairs actomyosin contractility and viscoelasticity, and elicits mitotic failures that trigger aneuploidy, mitosis-dependent DNA damage responses, p53 stabilization and premature differentiation. Importantly, reconstituting myosin activity is sufficient to restore mitotic fidelity, genome integrity, and balanced differentiation and stratification. Collectively, this study deciphers a mechanical signaling network in which Par3 acts upstream of Rho/ROCK-mediated actomyosin contractility to promote intrinsic force generation, thereby maintaining mitotic accuracy and cellular fitness at the genomic level. Disturbing this network may compromise not only epidermal homeostasis but potentially also that of other self-renewing epithelia.
Plasticity and environmental heterogeneity predict geographic resilience patterns of foundation species to future change
Authors: Telesca Luca , Peck Lloyd S. , Sanders Trystan , Thyrring Jakob , Sejr Mikael K. , Harper Elizabeth M.
Published: August 2018

Although geographic patterns of species’ sensitivity to global environmental changes are defined by interacting multiple stressors, little is known about the biological mechanisms shaping regional differences in organismal vulnerability. Here, we examine large-scale spatial variations in biomineralisation under heterogeneous environmental gradients of temperature, salinity and food availability across a 30° latitudinal range (3,334 km), to test whether plasticity in calcareous shell production and composition, from juveniles to large adults, mediates geographic patterns of resilience to climate change in critical foundation species, the musselsMytilus edulisandM. trossulus. We find mussels produced thinner shells with a higher organic content in polar than temperature regions, indicating decreasing shell calcification towards high latitudes. Salinity was the major driver of regional differences in mussel shell deposition, and in shell mineral and organic composition. In low-salinity environments, the production of calcite and organic shell layers was increased, providing higher resistance against dissolution in more corrosive waters. Conversely, under higher-salinity regimes, increased aragonite deposition suggests enhanced mechanical protection from predators. Interacting strong effects of decreasing salinity and increasing food availability on the compositional shell plasticity in polar and subpolar mussels during growth predict the deposition of a thicker external organic layer (periostracum) under forecasted future environmental conditions. This marked response potential ofMytilusspecies suggests a capacity for increased protection of high-latitude mussel populations from ocean acidification. Our work illustrates that mechanisms driving plastic responses to the spatial structure of multiple stressors can define geographic patterns of unforeseen species resilience to global environmental change.
Hepatocyte-Specific Hepatocyte Nuclear Factor 4 alpha (HNF4α) Deletion Decreases Resting Energy Expenditure By Disrupting Lipid and Carbohydrate Homeostasis
Authors: Huck Ian , Matthew Morris E. , Thyfault John , Apte Udayan
Published: August 2018

Hepatocyte Nuclear Factor 4 alpha (HNF4α) is required for hepatocyte differentiation and regulates expression of genes involved in lipid and carbohydrate metabolism including those that control VLDL secretion and gluconeogenesis. Whereas previous studies have focused on specific genes regulated by HNF4α in metabolism, its overall role in whole body energy utilization has not been studied. In this study, we used indirect calorimetry to determine the effect of hepatocyte-specific HNF4α deletion (HNF4α-KO) in mice on whole body energy expenditure (EE) and substrate utilization in fed, fasted, and high fat diet (HFD) conditions. HNF4α-KO had reduced resting EE during fed conditions and higher rates of carbohydrate oxidation with fasting. HNF4α-KO mice exhibited decreased body mass caused by fat mass depletion despite no change in energy intake and evidence of positive energy balance. HNF4α-KO mice were able to upregulate lipid oxidation during HFD suggesting that their metabolic flexibility was intact. However, only hepatocyte specific HNF4α-KO mice exhibited significant reduction in basal metabolic rate and spontaneous activity during HFD. Consistent with previous studies, hepatic gene expression in HNF4α-KO supports decreased gluconeogenesis and decreased VLDL export and hepatic β-oxidation in HNF4α-KO livers across all feeding conditions. Together, our data suggest deletion of hepatic HNF4α increases dependence on dietary carbohydrates and endogenous lipids for energy during fed and fasted conditions by inhibiting hepatic gluconeogenesis, hepatic lipid export, and intestinal lipid absorption resulting in decreased whole body energy expenditure. These data clarify the role of hepatic HNF4α on systemic metabolism and energy homeostasis.
Defining and Evaluating Microbial Contributions to Metabolite Variation in Microbiome-Metabolome Association Studies
Authors: Noecker Cecilia , Chiu Hsuan-Chao , McNally Colin P. , Borenstein Elhanan
Published: August 2018

Correlation-based analysis of paired microbiome-metabolome datasets is becoming a widespread research approach, aiming to comprehensively identify microbial drivers of metabolic variation. To date, however, the limitations of this approach have not been comprehensively evaluated. To address this challenge, we introduce a mathematical framework to quantify the contribution of each taxon to metabolite variation based on uptake and secretion fluxes. We additionally use a multi-species metabolic model to simulate simplified gut communities, generating idealized microbiome-metabolome datasets. We then compare observed taxon-metabolite correlations in these datasets to calculated ground-truth taxonomic contribution values. We find that in simulations of both a model 10-species community and of complex human gut microbiota, correlation-based analysis poorly identifies key contributors, with extremely low predictive value despite the idealized setting. We further demonstrate that the predictive value of correlation analysis is strongly influenced by both metabolite and taxon properties, as well as exogenous environmental variation. We finally discuss the practical implications of our findings for interpreting microbiome-metabolome studies.

Importance

Identifying the key microbial taxa responsible for metabolic differences between microbiomes is an important step towards understanding and manipulating microbiome metabolism. To achieve this goal, researchers commonly conduct microbiome-metabolome association studies, comprehensively measuring both the composition of species and the concentration of metabolites across a set of microbial community samples, and then testing for correlations between microbes and metabolites. Here, we evaluated the utility of this general approach by first developing a rigorous mathematical definition of the contribution of each microbial taxon to metabolite variation, and then examining these contributions in simulated datasets of microbial community metabolism. We found that standard correlation-based analysis of our simulated microbiome-metabolome datasets identifies true contributions with very low predictive value, and that its performance depends strongly on specific properties of both metabolites and microbes, as well as on the surrounding environment. Combined, our findings can guide future interpretation and validation of microbiome-metabolome studies.
Probing inhomogeneous diffusion in the microenvironments of phase-separated polymers under confinement
Authors: Shayegan Marjan , Tahvildari Radin , Kisley Lydia , Metera Kimberly , Michnick Stephen W. , Leslie Sabrina R.
Published: August 2018

Biopolymer condensates formed by liquid-liquid phase separation of proteins and nucleic acids have been recently discovered to be prevalent in biology. These dynamic condensates behave like biochemical reaction vessels but little is known about their structural organization and properties. Their biophysical properties and catalytic functions are likely related to condensate size, and thus it is critical that we study them on scales found in vivo. However, previous in vitro studies of condensate assembly and physical properties have involved condensates up to 1000 times larger than those found in vivo. Here, we report the application of confinement microscopy to visualize condensates and control their sizes by creating appropriate confinement length scales relevant to the cell environment. We observe anomalous diffusion of probe particles embedded within confined condensates, as well as heterogeneous dynamics in condensates formed from PEG/dextran and in ribonucleoprotein complexes of RNA and the RNA-binding protein Dhh1. We propose that the non-Gaussian dynamics we observe may indicate a hopping diffusion mechanism inside condensates. We also observe that for dextran-rich condensates, but not for ribonucleo condensates, probe particle diffusion depends on condensate size.
Hepatitis B mother-to-child transmission in the Eastern Region of Ghana: A cross-sectional pilot study
Authors: Hambridge Thomas , Nartey Yvonne , Duah Amoako , Plymoth Amelie
Published: August 2018

Background

Hepatitis B is a major health concern in Ghana, where prevalence of the virus remains high and most chronic patients are infected during childhood or at birth. There are several factors which can influence transmission risk from an infected mother to her infant, such as the presence of viral markers, the viral load and the use of prophylactic interventions. It is therefore important to determine the prevalence and main factors associated with mother-to-child transmission of hepatitis B in the context of Ghana.

Materials and methods

In this cross-sectional pilot study, hepatitis B testing was performed on infants born to infected mothers at a single site in the Eastern Region of Ghana. Test results were matched to a questionnaire which consisted of variables related to pregnancy and birth conditions. This was primarily a descriptive study to determine the prevalence of hepatitis B mother-to-child transmission as well as the preventive interventions and diagnostic methods used. The study variables were also analysed independently using Fisher’s exact test, while mother’s age at the time of delivery was assessed using univariate logistic regression.

Results

A total of 51 cases were included in the study and three (5.9%) of the infants tested positive. No significant association was observed between mother’s age and mother-to-child transmission (OR: 1.077, 95% CI: 0.828 – 1.403, p=0.58). A majority of infants received the standard hepatitis B vaccination schedule (96.1%) while two-thirds received the birth dose. There was no significant association observed between the clinical interventions reported in the study and mother-to-child transmission. Testing for viral markers and the use of antiviral therapy during pregnancy were absent in the population and could not be reliably assessed.

Conclusion

There was a low prevalence of HBV mother-to-child transmission observed despite a clear absence of viral marker and viral load testing. It is recommended that viral profile analysis is performed for hepatitis B positive pregnancies to identify high risk cases.
Role of STING complex in differential retrograde signaling in cybrids with K versus H haplogroup mtDNA
Authors: Schneider Kevin , Chwa Marilyn , Atilano Shari R. , Nashine Sonali , Udar Nitin , Boyer David S. , Jazwinski S. Michal , Miceli Michael V. , Nesburn Anthony B. , Kuppermann Baruch D. , Kenney M. Cristina
Published: August 2018

Mitochondrial (mt) DNA haplogroups, defined by specific single nucleotide polymorphism (SNPs) patterns, represent populations of diverse geographic origins and may play a role in disparate disease susceptibilities found in different ethnic/racial populations. The most common European haplogroup is H, while the K haplogroup is highly associated with Ashkenazi Jewish populations. Studies using transmitochondrial cybrids (cell lines with identical nuclei but mitochondria from either H or K haplogroup subjects) demonstrated significant molecular and biological differences but mechanisms for these disparities are unclear. In this study, we hypothesized that there is differential retrograde signaling occurring between the Stimulator of Interferon Genes (STING) pathway and H versus K mtDNA haplogroups. Results showed that K cybrids exhibit increased levels of cytoplasmic mtDNA fragments. After STING Knock-Down, H cybrids had lower expression levels for EGFR, BRCA1, DNMT3A, DNMT3B, HDAC1, and IFNα genes, but upregulated DNMT3A compared to control H cybrids. The STING-KD K cybrids showed downregulation of EGFR, DNMT3A, HDAC1, HCAD9, CFH, and CHI, along with upregulation of DNMT1 and IL-6 compared to control K cybrids. Since all cybrids have identical nuclei, the STING DNA sensor system interacts differently with K haplogroup mtDNA compared to H mtDNA for genes related to cancer (EGFR, BRCA1), methylation (DNMT1, DNMT3A, DNMT3B), acetylation (HDAC1, HDCA9), complement (CFH, CHI) and inflammation (IFNα, IL-6). In summary, in non-pathologic conditions, (a) STING is an important retrograde signaling mechanism(s) and (b) cybrids possessing Ashkenazi Jewish mtDNA (K haplogroup) interact with the STING complex differently compared to H cybrids which affects various disease-related pathways.
Cardiometabolic Recovery and Lactate Removal may be Related to Muscular Adaptations
Authors: Alarcón Meza Edgar Ismael , de Oliveira Glauber Lameira , de Oliveira Talita Adão Perini , Moreira Marcelo Hubner , Militão Angeliete Garcez , Filho José Fernandes , Da Silva Vernon Furtado , Martin Dantas Estélio Henrique , Valentim-Silva João Rafael
Published: August 2018

The aim of this study was to measure the differences in cardiorespiratory recovery (CR) and blood lactate removal among young athletes with differences in non-lactic (NP) and lactic anaerobic power (LP) and fatigue index (FI) but with the same degree of cardiorespiratory fitness. Sixteen swimmers from the Brazilian synchronized swimming team (2014) were divided into two groups GAP (Group High Power) (n = 9), with NP, LP, and FI (p<0.05) compared to GBP (Group Low Power) (n=7). Both groups performed a four-minute routine at competitive intensity. Anaerobic power, maximal heart rate (HR) and blood lactate (BL) were determined before and at 1, 3 and 5 minutes after the routine. Student’s t-test was used to analyze the intergroup differences of NP, LP, FI, maximum and lactic HR, and two-way ANOVA followed by Bonferroni was used to analyze HR and BL at 1, 3 and 5 minutes after activity with a significance of 5%. The FI of the GBP group was lower than that of the GAP group (P <0.05). The NP of the GBP group was higher than that of the GAP group (P <0.05). The maximum HR of the GBP group was equal to that of the GAP group (P> 0.05). The GBP group had better HR recovery than did the GAP group (P <0.05). BL had its lowest levels after 1 and 5 minutes of recovery in the GBP group when compared to the GAP group (P <0.05). The GBP group’s FI was significantly lower than that of the GAP group, while NP was higher, and CR was better in the GBP group, indicating a relationship between a lower FI and higher NP and LP with CR and suggesting that muscular adaptations have an important influence on CR and BL removal.
An open-source software analysis package for Microspheres with Ratiometric Barcode Lanthanide Encoding (MRBLEs)
Authors: Harink Björn , Nguyen Huy , Thorn Kurt , Fordyce Polly
Published: August 2018

Multiplexed bioassays, in which multiple analytes of interest are probed in parallel within a single small volume, have greatly accelerated the pace of biological discovery. Bead-based multiplexed bioassays have many technical advantages, including near solution-phase kinetics, small sample volume requirements, many within-assay replicates to reduce measurement error, and, for some bead materials, the ability to synthesize analytes directly on beads via solid-phase synthesis. To allow bead-based multiplexing, analytes can be synthesized on spectrally encoded beads with a 1:1 linkage between analyte identity and embedded codes. Bead-bound analyte libraries can then be pooled and incubated with a fluorescently-labeled macromolecule of interest, allowing downstream quantification of interactions between the macromolecule and all analytes simultaneously via imaging alone. Extracting quantitative binding data from these images poses several computational image processing challenges, requiring the ability to identify all beads in each image, quantify bound fluorescent material associated with each bead, and determine their embedded spectral code to reveal analyte identities. Here, we present a novel open-source Python software package (the mrbles analysis package) that provides the necessary tools to: (1) find encoded beads in a bright-field microscopy image; (2) quantify bound fluorescent material associated with bead perimeters; (3) identify embedded ratiometric spectral codes within beads; and (4) return data aggregated by embedded code and for each individual bead. We demonstrate the utility of this package by applying it towards analyzing data generated via multiplexed measurement of calcineurin protein binding to MRBLEs (Microspheres with Ratiometric Barcode Lanthanide Encoding) containing known and mutant binding peptide motifs. We anticipate that this flexible package should be applicable to a wide variety of assays, including simple bead or droplet finding analysis, quantification of binding to non-encoded beads, and analysis of multiplexed assays that use ratiometric, spectrally encoded beads.
Enterotype-like microbiome stratification as emergent structure in complex adaptive systems: A mathematical model
Authors: Martín Miguel Ángel
Published: August 2018

Background

Metagenomics has provided valuable insight into human gut microbiome composition together with its structure and function. Studies suggest that the adult gut microbial community possess a certain amount of stability and resilience. The architecture of host-microbial symbiotic states suggested by microbiome clustering findings and co-occurrence functional networks might be involved in these properties. Models for understanding the underlying structure (including enterotypes) and derived properties are in demand by researchers.

Principal findings

We propose a simple random function system as a model approach of the adaption and self-organization of the microbiome space when fostering the optimal functioning of the system. The construction of this model is based on key facts of microbiota functioning reported in recent studies. We aim to demonstrate the existence of a probability distribution as a microbiome attractor resulting from an intermittent adaption process. Its mathematical structural properties explain the stability of gut microbiota and its ability for restoration after occasional perturbations. The model is consistent with microbiome clustering results and provides precise mathematical meaning to the gradient among enterotypes previously reported. The model also explains how intermittent perturbations, such as long-term dietary patterns, might affect the microbiome structure, and these results are consistent with previously reported experimental results.

Conclusions/significance

These mathematical facts implied by the model unveil an underlying mechanism that may explain gut microbiome structure and related experimental findings. Within this framework, stability and resilience properties of human gut microbiota are explained as a consequence of the model.
Polycomb repressive complex 1 shapes the nucleosome landscape but not accessibility at target genes
Authors: King Hamish W. , Fursova Nadezda A. , Blackledge Neil P. , Klose Robert J.
Published: August 2018

Polycomb group (PcG) proteins are transcriptional repressors that play important roles in regulating gene expression during animal development. In vitro experiments have shown that PcG protein complexes can compact chromatin to limit the activity of chromatin remodeling enzymes and access of the transcriptional machinery to DNA. In fitting with these ideas, gene promoters associated with PcG proteins have been reported to be less accessible than other gene promoters. However, it remains largely untested in vivo whether PcG proteins define chromatin accessibility or other chromatin features. To address this important question, we examine the chromatin accessibility and nucleosome landscape at PcG protein-bound promoters in mouse embryonic stem cells using the assay for transposase accessible chromatin (ATAC)-seq. Combined with genetic ablation strategies, we unexpectedly discover that although PcG protein-occupied gene promoters exhibit reduced accessibility, this does not rely on PcG proteins. Instead, the Polycomb repressive complex 1 (PRC1) appears to play a unique role in driving elevated nucleosome occupancy and decreased nucleosomal spacing in Polycomb chromatin domains. Our new genome-scale observations argue, in contrast to the prevailing view, that PcG proteins do not significantly affect chromatin accessibility and highlight an underappreciated complexity in the relationship between chromatin accessibility, the nucleosome landscape, and PcG-mediated transcriptional repression.
Impaired translations: IFRS from English and annual reports into English
Authors: Nobes Christopher , Stadler Christian
Published: August 2018

Purpose

The purpose of this paper is to examine translation in the context of International Financial Reporting Standards (IFRS) by taking the example of the English term “impairment” in IAS 36, and following it into 19 translations. The paper then examines the terms used for impairment in English translations of annual reports provided by firms. Consideration is given to the best approach for translating regulations and whether that is also suitable for the translation of annual reports.

Design/methodology/approach

The two empirical parts of the paper involve: first, identifying the terms for impairment used in 19 official translations of IAS 36, and second, examining English-language translations of reports provided by 393 listed firms from 11 major countries.

Findings

Nearly all the terms used for “impairment” in translations of IAS 36 do not convey the message of damage to assets. In annual reports translated into English, many terms are misleading in that they do not mention impairment, peaking at 39 per cent in German and Italian reports in one year.

Research limitations/implications

Researchers should note that the information related to impairment in international databases is likely to contain errors, and the authors recommend that data should be hand-collected and then carefully checked by experts. The authors make suggestions for further research.

Practical implications

Translators of regulations should aim to convey the messages of the source documents, but translators of annual reports should not look only at the reports but also consult the terminology in the original regulations. The authors also suggest implications for regulators and analysts.

Originality/value

The paper innovates by separately considering regulations and annual reports. The authors examine a key accounting term systematically into a wide range of official translations. The core section of the paper is a new field of research: an empirical study of the translations of firms’ financial statements.
Accounting and the banality of evil
Authors: Antonelli Valerio , D’Alessio Raffaele , Rossi Roberto , Funnell Warwick
Published: August 2018

Purpose

The purpose of this paper is to identify the significant role of accounting in the expropriation of Jewish real estate after the enforcement of race laws under Benito Mussolini’s Fascist regime in Italy.

Design/methodology/approach

Hannah Arendt’s understanding of government bureaucracy in the twentieth century totalitarian regimes informs the research which draws upon a wide range of primary sources.

Findings

Implementation of the program of expropriation was the responsibility of a government body, EGELI, which was created specifically for this purpose. The language of accounting provided the means to disguise the nature and brutality of the process and allow bureaucrats to be removed from the consequences of their actions. Accounting reports from EGELI to the Ministry of Finance confirmed each year that those who worked in EGELI were devoted to its mission as an agency of the Fascist State.

Research limitations/implications

The findings of this study recognize the need for further research on the role played by servicemen, bureaucrats and accounting as a technology of government in the deportation of Italian Jews to Germany. The study also provides impetus to examine how other countries managed the properties confiscated or expropriated from the Jews in the earlier stages of the Final Solution.

Originality/value

The study is the first to identify the significant role played by accounting and accountants in the persecution of Italian Jews under the Fascism.
The use of food quality and prestige-based benefits for consumer segmentation
Authors: Heide Morten , Olsen Svein Ottar
Published: August 2018

Purpose

The purpose of this paper is to identify consumer segments based on the importance of food quality and prestige benefits when buying food for a special occasion; dinner party with friends.

Design/methodology/approach

Using cluster analysis, the importance of food quality benefits (quality, taste and health) and prestige benefits (prestige quality, hedonic, uniqueness, price and social) were investigated. The consumer segments were profiled using individual consumer characteristics (involvement in luxury, willingness to pay and socio-demographics).

Findings

Food quality benefits are the most important benefits when buying food for a party with friends and the authors identified four distinct consumer segments based on 20 different food quality and prestige benefits: perfectionists, premium, luxury seeking and value focussed. Three of the four consumer segments (perfectionists, premium and luxury seeking) find conventional food quality benefits important but differ in the importance they attribute to the different prestige benefits. The value focussed segment is not driven by prestige consumption but wants high quality at an affordable price.

Research limitations/implications

This study demonstrates that consumers are driven by different food and prestige benefits when buying food for a special occasion.

Originality/value

This study suggest some important differences between premium consumers, looking for food quality and hedonic benefits, and luxury seeking, with a relatively higher focus on prestige quality, uniqueness and social benefits. This study also identifies a significant distinction between perfectionists and value focussed consumers. Both segments are focussed on food quality benefits but differ in their focus on value and prestige benefits.
Measures aiding in identifying voluntarily helpful employees: an accounting student sample
Authors: Lyons Paul , Bandura Randall P.
Published: August 2018

Purpose

There have been few attempts to identify valid and efficient self-assessment measures for use by human resource practitioners or line managers to help distinguish job applicants and/or employees who may have a predisposition to offer voluntary helpful behavior, or contextual performance, on the job. This paper (exploratory and correlational) aims to identify measures that are positively and highly related to this valuable work behavior. Findings set the stage for further study and research aimed at creating predictive measures that possess reliable statistical properties.

Design/methodology/approach

Study design has two components: first, identity and analysis of measures of performance that are broadly supported in research literature; and second, correlational analysis of contextual performance measures with critical self-assessments. No effort to discover cause and effect linkages is reported; only relationships are disclosed.

Findings

Of the self-assessments examined, two (core self-evaluation and self-efficacy) were found to be positively and significantly related to valid measures of voluntary, helpful organizational behavior, in this case, measures of contextual performance and job dedication.

Research limitations/implications

The study made no attempt to establish statistically valid predictors of behavior. Sample size was relatively small and consisted of students preparing for a career in accounting.

Originality/value

Voluntary, helpful employee behavior is valuable in virtually all organizations. Isolated here are two brief and easy-to-administer self-assessments which may assist in the identification of individuals who possess an inclination to offer such behavior.
Mentors of preservice teachers
Authors: Lejonberg Eli , Elstad Eyvind , Sandvik Lise Vikan , Solhaug Trond , Christophersen Knut-Andreas
Published: August 2018

Purpose

The purpose of this paper is to discuss how different styles of mentoring in teacher education relate to mentor characteristics. Pre-service teachers often want practical advice. However, in Norway, school mentors have traditionally been encouraged to promote reflection rather than offering advice. This study seeks to explore the relationship between mentors’ support for reflection based and clear mentoring (a relatively direct approach to mentoring) and mentors’ self-efficacy and effort.

Design/methodology/approach

Using structural equation modelling of cross-sectional survey data (from 272 school mentors), the researchers in this study tested empirical interrelations between reflection-based mentoring, clear mentoring, mentor efficacy and effort. Clear mentoring was a reasonably consistent construct, while refection-based mentoring was a more elusive concept.

Findings

Effort was associated with support for reflection, while self-efficacy was moderately related to clear mentoring and reflection-based mentoring. The results illustrate that reflection-based methods are demanding for mentors. If direct approaches are more effective, additional evidence would be required to support mentor training that heavily emphasises reflection.

Research limitations/implications

Longitudinal and quasi-experimental studies are needed to support inferences about causality. Variable omission may have influenced the models. More research is needed to better understand the concept of reflection-based mentoring.

Originality/value

This paper contributes to the mentoring field by examining mentors’ preference for reflection based and clear mentoring and how such preferences are related to self-efficacy and effort. It also contributes to general and theoretical discussions about the relationships between beliefs about mentoring and mentor characteristics.