bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic analysis identifies molecular systems and biological pathways associated with household income
Authors: David Hill W. , Davies Neil M. , Ritchie Stuart J. , Skene Nathan G. , Bryois Julien , Bell Steven , Angelantonio Emanuele Di , Roberts David J. , Xueyi Shen , Davies Gail , Liewald David C.M. , Porteous David J. , Hayward Caroline , Butterworth Adam S. , McIntosh Andrew M. , Gale Catharine R. , Deary Ian J.
Published: March 2019

Socio-economic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. Previous genome-wide association studies (GWAS) using household income as a marker of SEP have shown that common genetic variants account for 11% of its variation. Here, in a sample of 286,301 participants from UK Biobank, we identified 30 independent genome-wide significant loci, 29 novel, that are associated with household income. Using a recently-developed method to meta-analyze data that leverages power from genetically-correlated traits, we identified an additional 120 income-associated loci. These loci showed clear evidence of functional enrichment, with transcriptional differences identified across multiple cortical tissues, in addition to links with GABAergic and serotonergic neurotransmission. We identified neurogenesis and the components of the synapse as candidate biological systems that are linked with income. By combining our GWAS on income with data from eQTL studies and chromatin interactions, 24 genes were prioritized for follow up, 18 of which were previously associated with cognitive ability. Using Mendelian Randomization, we identified cognitive ability as one of the causal, partly-heritable phenotypes that bridges the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. Significant differences between genetic correlations indicated that, the genetic variants associated with income are related to better mental health than those linked to educational attainment (another commonly-used marker of SEP). Finally, we were able to predict 2.5% of income differences using genetic data alone in an independent sample. These results are important for understanding the observed socioeconomic inequalities in Great Britain today.
The role of strigolactones in regulation of stomatal conductance and plant-pathogen interactions inArabidopsis thaliana
Authors: Kalliola Maria , Jakobson Liina , Davidsson Pär , Pennanen Ville , Waszczak Cezary , Yarmolinsky Dmitry , Zamora Olena , Palva E. Tapio , Kariola Tarja , Kollist Hannes , Brosché Mikael
Published: March 2019

Strigolactones are a group of phytohormones that control shoot branching inArabidopsis thaliana. However, in recent years they have been shown to affect many other plant processes. We previously showed that the strigolactone perception mutantmore axillary branches 2 (max2)has increased susceptibility to plant pathogenic bacteria as a result of more open stomata as well as alterations in hormonal signalling. Here we show that both, strigolactone biosynthesis- (max3andmax4), and perception mutants (max2anddwarf14) are significantly more sensitive toPseudomonas syringaeDC3000. Moreover, in response toP. syringaeinfection, high levels of SA accumulated inmax2and this mutant was ozone sensitive. To search for the mechanisms that could explain pathogen- and ozone sensitivity we performed gene expression analysis and several different assays that explore the function of guard cells and regulation of guard cell signalling.

Treatments with GR24 (a strigolactone analogue) resulted in very modest changes in defence-related gene expression. In contrast, guard cell function was clearly impaired inmax2and depending on the assay used, also inmax3, max4andd14mutants. Moreover, stomatal responses to stimuli that cause stomatal closure in wild-type plants (darkness, high CO2and ABA) were analysed in the strigolactone mutants. In darkness both strigolactone biosynthesis and perception mutants showed reduced stomatal closure, whereas the response to high CO2was impaired only inmax2andd14. The response to ABA was not impaired in any of the mutants. To position the role of MAX2 in the guard cell signalling network,max2was crossed with mutants defective in ABA biosynthesis (aba2), in guard cell ABA signalling (ost1) and a scaffold protein required for proper ion channel activity (ghr1). The stomatal conductance of double mutants was consistently higher than the corresponding single mutants, suggesting that MAX2 acts in a signalling pathway that functions in parallel to the well characterized guard cell ABA signalling pathway. We propose that the impaired defence responses ofmax2is related to more open stomata that allows increased entry of bacteria or air pollutants like ozone. Furthermore, as MAX2 appears to act in a specific branch of guard cell signalling (related to CO2signalling), this protein could be one of the elusive components that allow guard cells to distinguish between different environmental conditions.
Root caries on aParanthropus robustusthird molar from Drimolen
Authors: Towle Ian , Riga Alessandro , Irish Joel D. , Dori Irene , Menter Colin , Moggi-Cecchi Jacopo
Published: March 2019

Objectives

Dental caries is often perceived as a modern human disease. However, their presence is documented in many early human groups, various non-human primates and, increasingly, our hominin ancestors and relatives. In this study we describe an antemortem lesion on the root of aParanthropus robustusthird molar from Drimolen, South Africa, which likely represents another example of caries in fossil hominins.

Materials and Methods

The molar, DNH 40, is dated to 2.0–1.5 Ma and displays a lesion on the mesial root surface, extending from the cementoenamel junction 3 mm down toward the apex. The position and severity of the lesion was macroscopically recorded and micro-CT scanned to determine the extent of dentine involvement.

Results

A differential diagnosis indicates root caries, as the lesion is indistinguishable from clinical examples. Although necrotic in appearance, external tertiary dentine is evident on a micro CT scan. Gingival recession and/or continuous eruption of the tooth as a result of extensive occlusal wear would have occurred to facilitate caries formation. Therefore, the lesion is likely linked to relative old age of this individual.

Discussion

This new example increases the total number of carious lesions described inP. robustusteeth to 12, on occlusal, interproximal and, now, root surfaces. Beyond the consumption of caries-causing food(s), caries formation would have also required the presence of requisite intra-oral cariogenic bacteria in this individual and the species. Of interest, the presence of tertiary dentine on the outward surface suggests the DNH 40 lesion may have been arrested, i.e., no longer active, perhaps relating to a change in diet or oral microbiome just prior to the individual’s death.
A comprehensive atlas of immunological differences between humans, mice and non-human primates
Authors: Bjornson-Hooper Zachary B , Fragiadakis Gabriela K , Spitzer Matthew H , Madhireddy Deepthi , McIlwain Dave , Nolan Garry P
Published: March 2019

Animal models are an integral part of the drug development and evaluation process. However, they are unsurprisingly imperfect reflections of humans, and the extent and nature of many immunological differences are unknown. With the rise of targeted and biological therapeutics, it is increasingly important that we understand the molecular differences in immunological behavior of humans and model organisms. Thus, we profiled a large number of healthy humans, along with three of the model organisms most similar to humans: rhesus and cynomolgus macaques and African green monkeys; and the most widely used mammalian model: mice. Using cross-species, universal phenotyping and signaling panels, we measured immune cell signaling responses to an array of 15 stimuli using CyTOF mass cytometry. We found numerous instances of different cellular phenotypes and immune signaling events occurring within and between species with likely effects on evaluation of therapeutics, and detail three examples (double-positive T cell frequency and signaling; granulocyte response toBacillus anthracisantigen; and B cell subsets). We also explore the correlation of herpes simian B virus serostatus on the immune profile. The full dataset is available online athttps://flowrepository.org(accession FR-FCM-Z2ZY) andhttps://immuneatlas.org.
Relation of in-utero exposure to antiepileptic drugs to pregnancy duration and size at birth
Authors: Margulis Andrea V , Hernandez-Diaz Sonia , McElrath Thomas , Rothman Kenneth J , Plana Estel , Almqvist Catarina , D’Onofrio Brian M , Oberg Anna Sara
Published: March 2019

Background

The associations of individual antiepileptic drugs (AEDs) with pregnancy duration and size at birth, and potential dose relations, are not well characterized.

Methods

This cohort study used nationwide Swedish register data (1996-2013). Adjusting for smoking, epilepsy and other AED indications, we used linear and quantile regression to explore associations with pregnancy duration, and birth weight, length, and head circumference (the last three operationalized as z-scores). We used logistic regression for preterm delivery, small for gestational age, and microcephaly. Lamotrigine was the reference drug.

Results

6,720 infants were exposed to AEDs in utero; AED exposure increased over the study period. Relative to lamotrigine-exposed infants, carbamazepine-exposed infants were born, on average, 1.3 days earlier (mean [95% confidence interval]: −1.3 [−2.3 to −0.3]); were 0.1 standard deviations (SDs) lighter (−0.1 [−0.2 to 0.0]); and had a head circumference that was 0.2 SDs smaller (−0.2 [−0.3 to −0.1]). Pregabalin-exposed infants were born, on average, 1.1 days earlier (1.1 [−3.0 to 0.8]); were 0.1 SDs lighter (−0.1 [−0.3 to 0.0]); and had the same head circumference. Levetiracetam-exposed infants were born, on average, 0.5 days earlier (−0.5 [−2.6 to 1.6]); were 0. 1 SDs lighter (−0.1 [−0.3 to 0.0]); and were 0.1 SDs smaller (−0.1 [−0.3 to 0.1]) in head circumference. Valproic acid–exposed infants had, on average, the same duration of gestation and birth weight z-score, but were 0.2 SDs smaller (−0.2 [−0.2 to −0.1]) in head circumference. More negative associations at the left tail of pregnancy duration and birth weight z-score, effect-measure modification, and dose-response relations were noted for some of the associations. Observed associations were generally of smaller magnitude than that of smoking, assessed as a potential confounder in the same models.

Conclusions

In comparison with lamotrigine, valproic acid and carbamazepine had a more negative association with head circumference than other study AEDs.
Perceptions, attitudes and practices towards scabies in communities on the Bijagós Islands, Guinea-Bissau
Authors: Lopes Maria João , da Silva Eunice Teixeira , Ca Janete , Gonçalves Adriana , Rodrigues Amabelia , Manjuba Cristóvão , Nakutum Jose , D’Alessandro Umberto , Achan Jane , Logan James , Bailey Robin , Last Anna , Walker Steve , Marks Michael
Published: March 2019

Introduction

Scabies is highly endemic among impoverished populations and has been recently included in the WHO’s list of neglected tropical diseases (NTDs). Community support and behavioural changes are essential for the success of control interventions. This study aimed to explore beliefs, prevention attitudes and health care-seeking behaviours towards scabies in the Bijagós Archipelago of Guinea-Bissau.

Methods

Data were collected through two methods. Community key informants (community members, community health workers, healthcare workers and traditional healers) were interviewed using snowball sampling. A questionnaire covering perceptions, attitudes and practices was administered to community members using random cluster sampling. Thematic analysis of qualitative data was applied to identify themes. Descriptive statistics were used for quantitative data analysis.

Results

There was a satisfactory awareness about scabies, but perceptions about disease causation and transmission were imprecise. Misconceptions about personal hygiene as the primary measure for scabies prevention were recurrent. Some participants recognised the importance of early treatment to interrupt transmission. Treatment of close contacts was not considered important. Costs were the main determining factor for treatment choice between traditional healer and the local health centre. Late presentation and delayed treatment were common and associated with poverty and stigmatisation. Scabies impaired quality of life by affecting social interactions, health, fitness to work and school attendance.

Conclusions

There is a need to improve education, recognition, management and affordable access to treatment. Community education, healthcare workers’ training and skin NTDs integrated control programmes should address the challenges highlighted in this study.

Authors Summary

Scabies is a common skin infection in low income settings. We conducted a study in Guinea-Bissau to explore the knowledge, attitudes and practices about scabies. We conducted interviews with healthcare workers, traditional healers and community members and additionally used an oral-administered questionnaire with a larger sample of community residents. Most individuals had knowledge of scabies and were aware that person to person transmission occurred. However personal and environmental hygiene were both incorrectly identified as particularly important in the transmission of scabies. Cost played a major role in determining where individuals sought care and both poverty and disease associated stigma resulted in delays seeking care. There is a need to improve community and health care worker education about scabies and improve affordable access to treatment.
Estimating statistical power for event-related potential studies using the late positive potential
Authors: Gibney Kyla D. , Kypriotakis George , Cinciripini Paul M. , Robinson Jason D. , Minnix Jennifer A. , Versace Francesco
Published: March 2019

The late positive potential (LPP) is a common measurement used to study emotional processes of subjects in event-related potential (ERP) paradigms. Despite its extensive use in affective neuroscience, there is presently no gold standard for how to appropriately power ERP studies using the LPP in within-subject and between-subjects experimental designs. The present study investigates how the number of trials, number of subjects, and magnitude of the effect size affect statistical power in analyses of the LPP. Using Monte Carlo simulations of ERP experiments with varying numbers of trials, subjects, and effect sizes, we measured the probability of obtaining a statistically significant effect in 1,489 different experiments repeated 1,000 times each. Predictably, our results showed that statistical power increases with increasing numbers of trials and subjects and at larger effect sizes. In addition, we found that higher levels of statistical power can be achieved with lower numbers of subjects and trials and at lower effect sizes in within-subject than in between-subjects designs. Furthermore, we found that, as subjects are added to an experiment, the slope of the relationship between effect size and statistical power increases and shifts to the left until the power asymptotes to nearly 100% at higher effect sizes. This suggests that adding more subjects greatly increases statistical power at lower effect sizes (<1 µV) compared with more robust (>1.5 µV) effect sizes.
Towards accurate high-throughput ligand affinity prediction by exploiting structural ensembles, docking metrics and ligand similarity
Authors: Schneider Melanie , Pons Jean-Luc , Bourguet William , Labesse Gilles
Published: March 2019

Motivation

Nowadays, virtual screening (VS) plays a major role in the process of drug development. Nonetheless, an accurate estimation of binding affinities, which is crucial at all stages, is not trivial and may require target-specific fine-tuning. Furthermore, drug design also requires improved predictions for putative secondary targets among which is Estrogen Receptor alpha (ERα).

Results

VS based on combinations of Structure-Based VS (SBVS) and Ligand-Based VS (LBVS) is gaining momentum to help characterizing secondary targets of xenobiotics (including drugs and pollutants). In this study, we propose an integrated approach using ligand docking based on multiple structural en-sembles to reflect the conformational flexibility of the receptor. Then, we investigate the impact of the two different types of features (structure-based docking descriptors and ligand-based molecular descriptors) for affinity predictions based on a random forest algorithm. We find that ligand-based features have limited predictive power (rP=0.69,R2=0.47), compared to structure-based features (rP=0.78,R2=0.60) while their combination maintains the overall accuracy (rP=0.77,R2=0.56). Extending the training dataset to include xenobiotics, leads to a novel high-throughput affinity prediction method for ERαligands (rP=0.85,R2=0.71). Method’s robustness is tested on several ligand databases and performances are compared with existing rescoring procedures. The presented prediction tool is provided to the community as a dedicated satellite of the @TOME server.

Availability

http://atome4.cbs.cnrs.fr/ATOME_V3/SERVER/EDMon_v3.html

Contact

schneider@cbs.cnrs.fr,labesse@cbs.cnrs.fr
Dopamine transients delivered in learning contexts do not act as model-free prediction errors
Authors: Sharpe Melissa J. , Batchelor Hannah M. , Mueller Lauren E. , Chang Chun Yun , Maes Etienne J.P. , Niv Yael , Schoenbaum Geoffrey
Published: March 2019

Dopamine neurons fire transiently in response to unexpected rewards. These neural correlates are proposed to signal the reward prediction error described in model-free reinforcement learning algorithms. This error term represents the unpredicted or ‘excess’ value of the rewarding event. In model-free reinforcement learning, this value is then stored as part of the learned value of any antecedent cues, contexts or events, making them intrinsically valuable, independent of the specific rewarding event that caused the prediction error. In support of equivalence between dopamine transients and this model-free error term, proponents cite causal optogenetic studies showing that artificially induced dopamine transients cause lasting changes in behavior. Yet none of these studies directly demonstrate the presence of cached value under conditions appropriate for associative learning. To address this gap in our knowledge, we conducted three studies where we optogenetically activated dopamine neurons while rats were learning associative relationships, both with and without reward. In each experiment, the antecedent cues failed to acquired value and instead entered into value-independent associative relationships with the other cues or rewards. These results show that dopamine transients, constrained within appropriate learning situations, support valueless associative learning.
Structural Basis for the Clamping and Ca2+Activation of SNARE-mediated Fusion by Synaptotagmin
Authors: Grushin Kirill , Wang Jing , Coleman Jeff , Rothman James E. , Sindelar Charles E. , Krishnakumar Shyam S.
Published: March 2019

Synapotagmin-1 (Syt1) interacts with both SNARE proteins and lipid membranes to synchronize neurotransmitter release to Ca2+-influx. To understand the underlying molecular mechanism, we determined the structure of the Syt1-SNARE complex on lipid membranes using cryo-electron microscopy. Under resting conditions, the Syt1 C2 domains adopt a novel membrane orientation with a Mg2+-mediated partial insertion of the aliphatic loops, alongside weak interactions with the anionic lipid headgroups. The C2B domain concurrently binds the SNARE bundle via the ‘primary’ interface and is positioned between the SNAREpins and the membrane. In this configuration, Syt1 is projected to sterically delay the complete assembly of the associated SNAREpins and thus, contribute to clamping fusion. This Syt1-SNARE organization is disrupted upon Ca2+-influx as Syt1 reorients into the membrane, allowing the attached SNAREpins to complete zippering and drive fusion. Overall, we find cation (Mg2+/Ca2+) dependent membrane interaction is a key determinant of the dual clamp/activator function of Syt1.
The fitness cost and benefit of phase separated protein deposits
Authors: Sanchez de Groot Natalia , Burgas Marc Torrent , Ravarani Charles N. J. , Trusina Ala , Ventura Salvador , Babu M. Madan
Published: March 2019

Phase separation of soluble proteins into insoluble deposits is associated with numerous diseases. However, protein deposits can also function as membrane-less compartments for many cellular processes. What are the fitness costs and benefits of forming such deposits in different conditions? Using a model protein that phase separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast. The environmental condition and the cellular demand for the protein function emerge as key determinants of fitness. Protein deposit formation can lead to cell-to-cell differences in free protein abundance between individuals. This results in variable manifestation of protein function and a continuous range of phenotypes in a cell population, favoring survival of some individuals in certain environments. Thus, protein deposit formation by phase separation might be a mechanism to sense protein concentration in cells and to generate phenotypic variability. The selectable phenotypic variability, previously described for prions, could be a general property of proteins that can form phase separated assemblies and may influence cell fitness.

Stand-first text

Using a model protein that phase separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast.

Bullet points

The presented approach identifies and quantifies different fitness effects associated with protein deposit formation due to phase separation

The environmental condition and the cellular demand for the protein function emerge as key determinants of fitness upon protein deposit formation

Variability in protein deposit formation can lead to cell-to-cell differences in free protein abundance between individuals

Protein phase separation can generate a continuous range of phenotypes in a cell population
G1/S transcription factors assemble in discrete clusters that increase in number as cells grow
Authors: Black Labe , Tollis Sylvain , Fu Guo , Fiche Jean-Bernard , Dorsey Savanna , Cheng Jing , Ghazal Ghada , Notley Stephen , Crevier Benjamin , Bigness Jeremy , Nollmann Marcelo , Tyers Mike , Royer Catherine A.
Published: March 2019

The spatio-temporal organization of transcription factor (TF)-promoter interactions is critical for the coordination of transcriptional programs. In budding yeast, the main G1/S transcription factors, SBF and MBF, are limiting with respect to target promoters in small G1 phase cells and accumulate as cells grow, raising the question of how SBF/MBF are dynamically distributed across the G1/S regulon. Super-resolution Photo-Activatable Localization Microscopy (PALM) mapping of the static positions of SBF/MBF subunits revealed that 85% were organized into discrete clusters containing ∼8 copies regardless of cell size, while the number of clusters increased with growth. Stochastic simulations with a mathematical model based on co-localization of promoters in clusters recapitulated observed cluster behavior. A prediction of the model that SBF/MBF should exhibit both fast and slow dynamics was confirmed in PALM experiments on live cells. This spatio-temporal organization of the TFs that activate the G1/S regulon may help coordinate commitment to division.
Metformin rescues muscle function in BAG3 myofibrillar myopathy models
Authors: Ruparelia Avnika A. , McKaige Emily A. , Williams Caitlin , Schulze Keith E. , Fuchs Margit , Oorschot Viola , Lacene Emmanuelle , Mirella Meregalli , Baxter Emily C. , Torrente Yvan , Ramm Georg , Stojkovic Tanya , Lavoie Josée N. , Bryson-Richardson Robert J.
Published: March 2019

Dominant de novo mutations in the co-chaperone BAG3 cause a severe form of myofibrillar myopathy, exhibiting progressive muscle weakness, muscle structural failure, and protein aggregation.

To identify therapies we generated two zebrafish models, one conditionally expressing BAG3P209L and one with a nonsense mutation in bag3. Whilst transgenic BAG3P209L expressing fish display protein aggregation, modelling the early phase of the disease, bag3−/− fish demonstrate impaired autophagic activity, exercise dependent fibre disintegration, and reduced swimming activity, consistent with later stages.

We confirmed the presence of impaired autophagy in patient samples and screened autophagy promoting compounds for their effectiveness at removing protein aggregates, identifying nine including Metformin. Further evaluation demonstrated Metformin is not only able to remove the protein aggregates in zebrafish and human myoblasts but is also able to rescue the fibre disintegration and swimming deficit observed in the bag3−/− fish. Therefore, repurposing Metformin provides a promising therapy for BAG3 myopathy.
Overexpression of the Rieske FeS protein of the Cytochromeb6fcomplex increases C4photosynthesis
Authors: Ermakova Maria , Lopez-Calcagno Patricia E. , Raines Christine A. , Furbank Robert T. , von Caemmerer Susanne
Published: March 2019

C4plants contribute 20% to the global primary productivity despite representing only 4% of higher plant species. Their CO2concentrating mechanism operating between mesophyll and bundle sheath cells increases CO2partial pressure at the site of Rubisco and hence photosynthetic efficiency. Electron transport chains in both cell types supply ATP and NADPH for C4photosynthesis. Since Cytochromeb6fis a key point of control of electron transport in C3plants, we constitutively overexpressed the Rieske FeS subunit inSetaria viridisto study the effects on C4photosynthesis. Rieske FeS overexpression resulted in a higher content of Cytochromeb6fin both mesophyll and bundle sheath cells without marked changes in abundances of other photosynthetic complexes and Rubisco. Plants with higher Cytochromeb6fabundance showed better light conversion efficiency in both Photosystems and could generate higher proton-motive force across the thylakoid membrane. Rieske FeS abundance correlated with CO2assimilation rate and plants with a 10% increase in Rieske FeS content showed a 10% increase in CO2assimilation rate at ambient and saturating CO2and high light. Our results demonstrate that Cytochromeb6fcontrols the rate of electron transport in C4plants and that removing electron transport limitations can increase the rate of C4photosynthesis.
Forward modelling reveals dynamics of neural orientation tuning to unconscious visual stimuli during binocular rivalry
Authors: Tang Matthew F. , Arabzadeh Ehsan , Mattingley Jason B.
Published: March 2019

When different visual stimuli are presented to the two eyes, they typically compete for access to conscious perception, a phenomenon known as binocular rivalry. Previous studies of binocular rivalry have shown that neural responses to consciously suppressed stimuli are markedly diminished in magnitude, though they may still be encoded to some extent. Here we employed multivariate forward modelling of human electroencephalography (EEG) data to quantify orientation-selective responses to visual gratings during binocular rivalry. We found robust orientation tuning to both conscious and unconscious gratings. This tuning was enhanced for the suppressed stimulus well before it was available for conscious report. The same pattern was evident in the overall magnitude of neural responses, and it emerged even earlier than the changes in neural tuning. Taken together, our findings suggest that rivalry suppression affects broadband, non-orientation selective aspects of neural activity before refining fine-grained feature-selective information.
Entrainment of local synchrony reveals a causal role for high-beta right frontal oscillations in human visual consciousness
Authors: Vernet Marine , Stengel Chloé , Quentin Romain , Amengual Julià L. , Valero-Cabré Antoni
Published: March 2019

Prior evidence supports the critical role of oscillatory activity in cognitive function, but are cerebral oscillations simply correlated or causally linked to specific aspects of visual cognition? Here, EEG signals were recorded on humans performing a conscious visual detection task, while they received briefrhythmicorrandomnoninvasive stimulation patterns delivered to the right Frontal Eye Field prior to the onset of a lateralized target. Compared torandompatterns,rhythmichigh-beta patterns led to greater entrainment of local oscillations (i.e., increased power and phase alignment at the stimulation frequency), and to higher conscious detection of contralateral targets. When stimulation succeeded in enhancing visual detection, the magnitude of oscillation entrainment correlated with visual performance increases. Our study demonstrates a causal link between high-beta oscillatory activity in the Frontal Eye Field and conscious visual perception. Furthermore, it supports future applications of brain stimulation to manipulate local synchrony and improve or restore impaired visual behaviors.
Genome-wide profiling of microRNAs and prediction of mRNA targets in 17 bovine tissues
Authors: Wang Min , Chamberlain Amanda J , Prowse-Wilkins Claire P , Vander Jagt Christy J , Hancock Timothy P , Pryce Jennie E , Cocks Benjamin G , Goddard Mike E , Hayes Benjamin J
Published: March 2019

MicroRNAs regulate many eukaryotic biological processes in a temporal- and spatial-specific manner. Yet in cattle it is not fully known which microRNAs are expressed in each tissue, which genes they regulate, or which sites a given microRNA bind to within messenger RNAs. An improved annotation of tissue-specific microRNA network may in the future assist with the identification of causal variants affecting complex traits. Here, we report findings from analysing short RNA sequence from 17 tissues from a single lactating dairy cow. Using miRDeep2, we identified 699 expressed mature microRNA sequences. Using TargetScan, known (60%) and novel (40%) microRNAs were predicted to interact with 780,481 sites in bovine messenger RNAs homologous with human. Putative interactions between microRNA families and targets were significantly enriched for interactions from previous experimental and computational identification. Characterizing features of microRNAs and targets, we showed that (1) mature microRNAs derived from different arms of the same precursor targeted different genes in different tissues; (2) miRNA target sites preferentially occurred within gene regions marked with active histone modification; (3) variants within microRNAs and targets had lower allele frequencies than variants across the genome, as identified from 65 million whole genome sequence variants; (4) no significant correlation was found between the abundance of microRNAs and messenger RNAs differentially expressed in the same tissue; (5) microRNAs and target sites weren’t significantly associated with allelic imbalance of gene targets. This study contributes to the goals of Functional Annotation of Animal Genomes consortium to improve the annotation of genomes of domestic animals.
Is microbial activity in tropical forests limited by phosphorus availability? Evidence from a tropical forest in China
Authors: Mori Taiki , Lu Xiankai , Wang Cong , Mao Qinggong , Wang Senhao , Zhang Wei , Mo Jiangming
Published: March 2019

The prevailing paradigm for soil microbial activity in tropical forests is that microbial activity is limited by phosphorus (P) availability. Thus, exogenous P addition should increase rates of organic matter decomposition. Studies have also confirmed that soil respiration is accelerated when P is added experimentally. However, we hypothesize that the increased rates of soil microbial respiration could be due to the release of organic material from the surface of soil minerals when P is added, because P is more successful at binding to soil particles than organic compounds. In this study, we demonstrate that P addition to soil is associated with significantly higher dissolved organic carbon (DOC) content in a tropical evergreen forest in southern China. Our results indicate that P fertilization stimulated soil respiration but suppressed litter decomposition. Results from a second sorption experiment revealed that the recovery ratio of added DOC in the soil of a plot fertilized with P for 9 years was larger than the ratio in the soil of a non-fertilized plot, although the difference was small. We also conducted a literature review on the effects of P fertilization on the decomposition rates of litter and soil organic matter at our study site. Previous studies have consistently reported that P addition led to higher response ratios of soil microbial respiration than litter decomposition. Therefore, experiments based on P addition cannot be used to test whether microbial activity is P-limited in tropical forest soils, because organic carbon desorption occurs when P is added. Our findings suggest that the prevailing paradigm on the relationship between P and microbial activity in tropical forest soils should be re-evaluated.
Establishment of an orthodontic retention mouse model and the effect of anti-c-Fms antibody on orthodontic relapse
Authors: Qi Jiawei , Kitaura Hideki , Shen Wei-Ren , Kishikawa Akiko , Ogawa Saika , Ohori Fumitoshi , Noguchi Takahiro , Marahleh Aseel , Nara Yasuhiko , Mizoguchi Itaru
Published: March 2019

Orthodontic relapse after orthodontic treatment is a major clinical issue in the dental field. However, the biological mechanism of orthodontic relapse is still unclear. This study aimed to establish a mouse model of orthodontic retention to examine how retention affects the rate and the amount of orthodontic relapse. We also sought to examine the role of osteoclastogenesis in relapse using an antibody to block the activity of M-CSF, an essential factor of osteoclast formation. Mice were treated with a nickel-titanium closed-coil spring that was fixed between the upper incisors and the upper-left first molar to move the first molar in a mesial direction over 12 days. Mice were randomly divided into three groups: group 1, no retention (G1); group 2, retention for 2 weeks (G2); and group 3, retention for 4 weeks (G3). In G2 and G3, a light-cured resin was placed in the space between the first and second molars as a model of retention. Orthodontic relapse was assessed by measuring changes in the dimensions of the gap created between the first and second molars. To assess the activity and role of osteoclasts, mice in G3 were injected with anti-c-Fms antibody or PBS, and assessed for changes in relapse distance and rate. Overall, we found that a longer retention period was associated with a slower rate of relapse and a shorter overall amount of relapse. In addition, inhibiting osteoclast formation using the anti-c-Fms antibody also reduced orthodontic relapse. These results suggest that M-CSF and/or its receptor could be potential therapeutic targets in the prevention and treatment of orthodontic relapse.
Association between hot flashes severity and oxidative stress among Mexican postmenopausal women: a cross-sectional study
Authors: Sánchez-Rodríguez Martha A. , Zacarías-Flores Mariano , Arronte-Rosales Alicia , Mendoza-Núñez Víctor Manuel
Published: March 2019

Objective

To assess the association between hot flashes (HFs) severity and oxidative stress (OS) in Mexican postmenopausal women.

Methods

A cross-sectional study was carried out with perimenopausal women aged 40-59 years community-dwelling from Mexico City, Mexico. They participated in Menopause and Oxidative Stress Project. The baseline sample consisted of 476 women recruited to participate; 161 women were excluded due to different reasons. Hence, 315 women were selected to establish two groups, a) 145 premenopausal women (yet with menstrual bleeding), and b) 170 postmenopausal women (without menses). All women were free of cardiovascular, kidney, hepatic or cancer disease, and without antioxidant supplement intake for at least six months prior to the beginning of the study; none had previously received hormone therapy. As OS markers, we measured plasma malondialdehyde using the TBARS assay, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), uric acid, and total antioxidant status; also, we calculated SOD/GPx ratio, antioxidant gap and an oxidative stress score ranging from 0 to 7. The HFs were evaluated using the Menopause Rating Scale. The women completed Spanish version of the Athens Insomnia Scale, Zung Self-Rating Anxiety Scale and Zung Self-Rating Depression Scale and a questionnaire of pro-oxidant factors.

Results

Stress score increased with HFs severity (mild 2.9±0.23, moderate 3.1±0.21 and severe 3.8±0.18, p<0.01) in postmenopausal women. We observed a positive correlation between HFs severity and stress score, r=0.247 (p=0.001) in postmenopausal women; other test scores were not correlated. Severe HFs were a risk factor for OS (OR=3.37, 95%CI: 1.20-9.51, p<0.05) in an adjusted multivariate analysis by different postmenopausal symptoms and pro-oxidant factors; we did not see any association in premenopausal women.

Conclusion

Our findings suggest an association between HFs severity and OS in Mexican postmenopausal women.
Oscillations of MyoD and Hes1 proteins regulate the maintenance of activated muscle stem cells
Authors: Lahmann Ines , Bröhl Dominique , Zyrianova Tatiana , Isomura Akihiro , Czajkowski Maciej T. , Kapoor Varun , Griger Joscha , Ruffault Pierre-Louis , Mademtzoglou Despoina , Zammit Peter S. , Wunderlich Thomas , Spuler Simone , Kühn Ralf , Preibisch Stephan , Wolf Jana , Kageyama Ryoichiro , Birchmeier Carmen
Published: March 2019

The balance between proliferation and differentiation of muscle stem cells is tightly controlled, ensuring the maintenance of a cellular pool needed for muscle growth and repair. We demonstrate here that the transcriptional regulator Hes1 controls the balance between proliferation and differentiation of activated muscle stem cells in both developing and regenerating muscle. We observed that Hes1 is expressed in an oscillatory manner in activated stem cells where it drives the oscillatory expression of MyoD. MyoD expression oscillates in activated muscle stem cells from postnatal and adult muscle under various conditions: when the stem cells are dispersed in culture, when they remain associated with single muscle fibers, or when they reside in muscle biopsies. Unstable MyoD oscillations and long periods of sustained MyoD expression are observed in differentiating cells. Ablation of the Hes1 oscillator in stem cells interfered with stable MyoD oscillations and led to prolonged periods of sustained MyoD expression, resulting in increased differentiation propensity. This interfered with the maintenance of activated muscle stem cells, and impaired muscle growth and repair. We conclude that oscillatory MyoD expression allows the cells to remain in an undifferentiated and proliferative state and is required for amplification of the activated stem cell pool.
An approach to generating the sequence of part variant design based on information transfer utility
Authors: Xu Xinsheng , Lin Jing , Xiao Ying , Yu Jianzhe , Liu Qing , Geng Jie
Published: March 2019

Purpose

Product variant design can only be achieved after all its constituent parts have been implemented by variant design. It is necessary to plan the sequence of part variant design reasonably. The product variant design process involves a large amount of information transfer events at the dimensional level. A reasonable product variant design process needs to make full use of the information transfer characters of parts to decrease the uncertainty of product variant design process. The existing methods of researching the product variant design process mainly focus on resource constraint and activity logic. They are deficient, however, in information transfer resolution and uncertainty management. This paper aims to address these issues.

Design/methodology/approach

This paper identifies the number of dimension transfer paths and the position of dimension locating within a transfer path as being the key factors affecting the information transfer role of dimension. Information transfer utility is proposed to measure the information transfer capability of dimensions and parts. Based on these, a two-stage approach of generating the sequence of part variant design based on information transfer utility is proposed.

Findings

The uncertainty of dimension constraint network is minimal during the product variant design process when parts are implemented by variant design under the sequence generated through a two-stage method based on the information transfer utilities of parts, as does the times of parameter transferring and iteration in dimension constraint network.

Originality/value

Part variant design under the sequence of descending information transferring utilities can decrease the difficulty of implementing product variant design validly and also increase the efficiency. This suggests an innovative method to planning the product variant design process reasonably from the perspective of informatics.
Robust task-space tracking for free-floating space manipulators by cerebellar model articulation controller
Authors: Li Liang , Chen Ziyu , Wang Yaobing , Zhang Xiaodong , Wang Ningfei
Published: March 2019

Purpose

The purpose of this paper is to solve the tracking problem for free-floating space manipulators (FFSMs) in task space with parameter uncertainties and external disturbance.

Design/methodology/approach

In this paper, the novel cerebellar model articulation controller (CMAC) is designed with the feedback controller. More precisely, the parameter uncertainties in the FFSM are considered for achieving the robustness.

Findings

By using the dynamically equivalent model, the CMAC can be designed and trained with the desired performance, such that the prescribed trajectory can be followed accordingly. The simulation results are presented for illustrating the validity of the derived results.

Originality/value

Based on the designed CMAC, the tracking error would be approaching zero by choosing appropriate quantization level in CMAC and the corresponding learning rules can be tuned online.
Impact of training in Autism on inclusive practices
Authors: Nolan Amy Dympna , Hannah Elizabeth Fraser Selkirk
Published: March 2019

Purpose

The purpose of this paper is to evaluate the impact of training on educational staff attitudes, sentiments, concerns and efficacy in providing support for children with Autism in mainstream settings.

Design/methodology/approach

The investigation adopted a pre-test/post-test, quasi-experimental, within-subject research design. In total, 35 early years educators, teachers and pupil support assistants from one Scottish Local Authority (LA) undertook training delivered by the LA’s Communication and Language Outreach Service. Measures included the Sentiments, Attitudes, and Concerns about Inclusive Education Revised (SACIE-R) scale and the teacher efficacy for inclusive practices (TEIP) scale pre and post-training. Post-training participants completed a questionnaire employing open and closed questions to assess perceived usefulness of training, application of knowledge and effectiveness of the teaching strategies.

Findings

Combining data from the three sectors there was a significant change in staff efficacy for inclusive practices (z=−3.406, p=0.001, p<0.05, with a medium effect size r=0.41) although there were differences between the sectors. There was a significant change in SACIE-R total scores (z=−3.945, p=0.000, p<0.05; with a medium effect size r=0.47), sentiments (z=−2.763, p=0.006, p<0.05; with a medium effect size r=0.33) and concerns (z=−3.685, p=0.000, p<0.05; with a medium effect size of r=0.44) subscale scores for the combined sector data. There was no significant change in the attitudes subscale scores for the combined sector data (z=−1.106, p=2.69, p>0.05; with a small effect size r=0.13) although there were differences between the sectors.

Research limitations/implications

Limitations include: small sample size, minor differences in the training in different sectors, purposeful sampling, use of questionnaire post-training, variability of completion of SCAIE-R and TEIP post-training.

Originality/value

There appears to be limited research into inclusive practices for children with Autism in the UK context, which this study aims to address.
A theory of enterprise risk management
Authors: Jankensgård Håkan
Published: March 2019

Purpose

The purpose of this paper is to develop a theory of enterprise risk management (ERM).

Design/methodology/approach

The method is to develop a theory for ERM based on identifying the general risk management problems that it is supposed to solve and to apply the principle of deduction based on these premises.

Findings

ERM consists of risk governance, which is a set of mechanisms that deals with the agency problem of risk management and risk aggregation, which is a set of mechanisms that deals with the information problem of risk management.

Research limitations/implications

The theory, by identifying the central role of the Board of Directors, encourages further research into the capabilities and incentives of directors as determinants of ERM adoption. It also encourages research into how ERM adoption depends on proxies for agency problems of risk management, such as a decentralized company structure.

Practical implications

The theory encourages Boards of Directors to focus on understanding where the under and over management of risk are likely to be greatest, as opposed to the current practice of mapping a large number of risk factors.

Originality/value

The theory complements existing theory on corporate risk management, which revolves around the role of external frictions, by focusing on internal frictions in the firm that prevent effective risk management. It is the first work to delineate ERM vis-a-vis existing risk theory.