bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying metacognitive thresholds using signal-detection theory
Authors: Sherman M.T. , Seth A.K. , Barrett A.B
Published: July 2018

How sure are we about what we know? Confidence, measured via self-report, is often interpreted as a subjective probabilistic estimate on having made a correct judgement. The neurocognitive mechanisms underlying the construction of confidence and the information incorporated into these judgements are of increasing interest. Investigating these mechanisms requires principled and practically applicable measures of confidence and metacognition. Unfortunately, current measures of confidence are subject to distortions from decision biases and task performance. Motivated by a recent signal-detection theoretic behavioural measure of metacognitive sensitivity, known as meta-ď, here we present a quantitative behavioural measure of confidence that is invariant to decision bias and task performance. This measure, which we call m-distance, captures in a principled way the propensity to report decisions with high (or low) confidence. Computational simulations demonstrate the robustness of m-distance to decision bias and task performance, as well as its behaviour under conditions of high and low metacognitive sensitivity and under dual-channel and hierarchical models of metacognition. The introduction of the m-distance measure will enhance systematic quantitative studies of the behavioural expression and neurocognitive basis of subjective confidence.
Mitogen-Activated Protein Kinase-Dependent Fiber-Type Regulation in Skeletal Muscle
Authors: Boyer Justin G. , Song Taejeong , Lee Donghoon , Fu Xing , Sadayappan Sakthivel , Molkentin Jeffery D.
Published: July 2018

Mitogen-activated protein kinases (MAPK) are conserved protein kinases that regulate a diverse array of cellular activities. Stress or mitogenic signals activate three primary branches of the greater MAPK cascade, each of which consists of a phosphorylation-dependent array of successively acting kinases. The extracellular signal-regulated kinase 1/2 (ERK1/2) branch is regulated by growth factory signaling at the cell membrane, leading to phosphorylation of the dual-specificity kinase MEK1, which is dedicated to ERK1/2 phosphorylation. Previous studies have established a link between MAPK activation and endurance exercise, but whether a single MAPK is responsible for establishing muscle metabolic fate is unclear. Using mouse genetics we observed that muscle-specific expression of a constitutively active MEK1 promotes greater ERK1/2 signaling that mediates fiber-type switching in mouse skeletal muscle to a slow, oxidative phenotype with type I myosin heavy chain expression. Induced expression of the activated MEK1 mutant using either a MyoD-Cre or myosin light chain-Cre strategy equally increased the number of type I fibers in skeletal muscle with significantly reduced size compared to controls. Moreover, activation of MEK1 in mature myofibers of an adult mouse using a transgene containing a tamoxifen inducible MerCreMer cDNA under the control of a skeletal α-actin promoter produced a similar phenotype of switching towards a slow-oxidative program. Physiologic assessment of mice with greater skeletal muscle slow-oxidative fibers showed enhanced metabolic activity and oxygen consumption with greater fatigue resistance of individual muscles. In summary, these results show that sustained MEK1-ERK1/2 activity in skeletal muscle produces a fast-to-slow fiber-type switch, suggesting that modulation of this signaling pathway may represent a therapeutic approach to enhance the long-term metabolic effectiveness of musclein vivo.
A Universal Probe Set for Targeted Sequencing of 353 Nuclear Genes from Any Flowering Plant Designed Using k-medoids Clustering
Authors: Johnson Matthew G. , Pokorny Lisa , Dodsworth Steven , Botigue Laura R. , Cowan Robyn S. , Devault Alison , Eiserhardt Wolf L. , Epitawalage Niroshini , Forest Félix , Kim Jan T. , Leebens-Mack James H. , Leitch Ilia J. , Maurin Olivier , Soltis Douglas E. , Soltis Pamela S. , Wong Gane Ka-Shu , Baker William J. , Wickett Norman J.
Published: July 2018

Sequencing of target-enriched libraries is an efficient and cost-effective method for obtaining DNA sequence data from hundreds of nuclear loci for phylogeny reconstruction. Much of the cost associated with developing targeted sequencing approaches is preliminary data needed for identifying orthologous loci for probe design. In plants, identifying orthologous loci has proven difficult due to a large number of whole-genome duplication events, especially in the angiosperms (flowering plants). We used multiple sequence alignments from over 600 angiosperms for 353 putatively single-copy protein-coding genes to design a set of targeted sequencing probes for phylogenetic studies of any angiosperm lineage. To maximize the phylogenetic potential of the probes while minimizing the cost of production, we introduce a k-medoids clustering approach to identify the minimum number of sequences necessary to represent each coding sequence in the final probe set. Using this method, five to 15 representative sequences were selected per orthologous locus, representing the sequence diversity of angiosperms more efficiently than if probes were designed using available sequenced genomes alone. To test our approximately 80,000 probes, we hybridized libraries from 42 species spanning all higher-order lineages of angiosperms, with a focus on taxa not present in the sequence alignments used to design the probes. Out of a possible 353 coding sequences, we recovered an average of 283 per species and at least 100 in all species. Differences among taxa in sequence recovery could not be explained by relatedness to the representative taxa selected for probe design, suggesting that there is no phylogenetic bias in the probe set. Our probe set, which targeted 260 kbp of coding sequence, achieved a median recovery of 137 kbp per taxon in coding regions, a maximum recovery of 250 kbp, and an additional median of 212 kbp per taxon in flanking non-coding regions across all species. These results suggest that the Angiosperms353 probe set described here is effective for any group of flowering plants and would be useful for phylogenetic studies from the species level to higher-order lineages, including all angiosperms.
Start-Stop Assembly: a functionally scarless DNA assembly system optimised for metabolic engineering
Authors: Taylor George M. , Mordaka Paweł M. , Heap John T.
Published: July 2018

DNA assembly allows individual DNA constructs or designed mixtures to be assembled quickly and reliably. Most methods are either: (i) Modular, easily scalable and suitable for combinatorial assembly, but leave undesirable ‘scar’ sequences; or (ii) bespoke (non-modular), scarless but less suitable for construction of combinatorial libraries. Both have limitations for metabolic engineering. To overcome this trade-off we devised Start-Stop Assembly, a multi-part, modular DNA assembly method which is both functionally scarless and suitable for combinatorial assembly. Crucially, 3 bp overhangs corresponding to start and stop codons are used to assemble coding sequences into expression units, avoiding scars at sensitive coding sequence boundaries. Building on this concept, a complete DNA assembly framework was designed and implemented, allowing assembly of up to 15 genes from up to 60 parts (or mixtures); monocistronic, operon-based or hybrid configurations; and a new streamlined assembly hierarchy minimising the number of vectors. Only one destination vector is required per organism, reflecting our optimisation of the system for metabolic engineering in diverse organisms. Metabolic engineering using Start-Stop Assembly was demonstrated by combinatorial assembly of carotenoid pathways inE. coliresulting in a wide range of carotenoid production and colony size phenotypes indicating the intended exploration of design space.

GRAPHICAL ABSTRACT
Lateral Root Priming Synergystically Arises from Root Growth and Auxin Transport Dynamics
Authors: van den Berg Thea , ten Tusscher Kirsten H.
Published: July 2018

The root system is a major determinant of plant fitness. Its capacity to supply the plant with sufficient water and nutrients strongly depends on root system architecture, which arises from the repeated branching off of lateral roots. A critical first step in lateral root formation is priming, which prepatterns sites competent of forming a lateral root. Priming is characterized by temporal oscillations in auxin, auxin signalling and gene expression in the root meristem, which through growth become transformed into a spatially repetitive pattern of competent sites. Previous studies have demonstrated the importance of auxin synthesis, transport and perception for the amplitude of these oscillations and their chances of producing an actual competent site. Additionally, repeated lateral root cap apoptosis was demonstrated to be strongly correlated with repetitive lateral root priming. Intriguingly, no single mutation has been identified that fully abolishes lateral root formation, and thusfar the mechanism underlying oscillations has remained unknown. In this study, we investigated the impact of auxin reflux loop properties combined with root growth dynamics on priming, using a computational approach. To this end we developed a novel multi-scale root model incorporating a realistic root tip architecture and reflux loop properties as well as root growth dynamics. Excitingly, in this model, repetitive auxin elevations automatically emerge. First, we show that root tip architecture and reflux loop properties result in an auxin loading zone at the start of the elongation zone, with preferential auxin loading in narrow vasculature cells. Second, we demonstrate how meristematic root growth dynamics causes regular alternations in the sizes of cells arriving at the elongation zone, which subsequently become amplified during cell expansion. These cell size differences translate into differences in cellular auxin loading potential. Combined, these properties result in temporal and spatial fluctuations in auxin levels in vasculature and pericycle cells. Our model predicts that temporal priming frequency predominantly depends on cell cycle duration, while cell cycle duration together with meristem size control lateral root spacing.
Instability in 18S and 5.8S rDNA copy numbers and 18S:5.8S ratios in longitudinally-collected human DNA samples detected by monochrome multiplex qPCR
Authors: Ligerman Chris B. , Baird Lisa , Leppert Mark F. , Cawthon Richard M.
Published: July 2018

Ribosomal DNA encodes the structural RNAs of the ribosomes. Ribosomal DNA instability is a major contributor to aging in yeast, but its role in human aging and longevity is largely unknown. Human 45S rDNA encodes the 18S, 5.8S, and 28S ribosomal RNAs; ranges in copy number from 60 to > 800 per cell, distributed as tandem repeats along the short arms of the five acrocentric chromosomes (p13, p14, p15, p21, and p22); and is prone to frequent homologous and non-homologous recombination. Here we present two multiplex quantitative PCR assays, one for 18S rDNA normalized to the single copy gene beta-globin (HBB), and the other for 5.8S rDNA normalized to the single copy gene albumin (ALB). Longitudinally-collected pairs of DNAs from bloods drawn approximately 16 years apart from 40 females and 39 males, aged < 1 to 77 years at first blood draw, from the Utah CEPH families were assayed. Ribosomal DNA copy number varied over a four-fold range between subjects and increased approximately 14% across the lifespan. Longitudinal within-individual gains in copy number up to +68% and losses down to ‐25% were observed, while repeated assays of single DNA samples varied approximately +/- 10%. While 18S and 5.8S rDNA tended to be gained and lost together, the 18S:5.8S ratio was also unstable longitudinally, with increases up to +19% and decreases down to ‐15% observed. The 18S:5.8S ratio at second draw, relative to that at first draw, increased significantly across the lifespan in males, but not in females. To our knowledge this is the first report of within-individual longitudinal changes in the human 18S and 5.8S rDNA copy numbers. These assays will facilitate investigations of the biology of ribosomal RNA genes and their roles in health and disease across the human lifespan.
Mitochondrial genetics of exceptional longevity in multigeneration matrilineages
Authors: Kerber Richard A. , O’Brien Elizabeth , Munger Ron , Smith Ken R. , Cawthon Richard M.
Published: July 2018

Some heritable mitochondrial DNA (mtDNA) sequence variants may slow the rate of aging. The European mitochondrial haplogroup K has previously been reported to be increased in frequency in centenarians and nonagenarians relative to its frequency in younger individuals, by standard case/control study designs. To select for mitochondrial genomes likely to carry beneficial genetic variants, we screened a large genealogical database (the Utah Population Database, UPDB) for mitochondrial lineages in which the frequency of survival past 90 years was significantly higher than in the general population, and also significantly higher than in close non-matrilineal relatives. We ranked 14,900 distinct matrilineages by the strength of their association with longevity. Full sequencing of the mtDNAs from a single individual from each of 53 matrilineages in the top longevity ranks and each of 374 control matrilineages from the general Utah population, followed by analyses of the mtDNA haplogroup frequencies, identified haplogroup K2 as the haplogroup most enriched in frequency by the longevity selection (Odds Ratio = 23.05). We then analyzed overall survival and cause-specific mortality in the several thousand individuals aged 40 years or older whose mtDNA genotypes could be imputed from the 374 fully sequenced control mtDNAs. In these control matrilineages Haplogroup K2 individuals (n=332) enjoyed a significantly lower all-cause mortality risk than the general population (HR=0.81), attributable in part to a significantly lower risk of dying from heart disease (HR=0.50), as well as lower (though not significantly lower) risks of dying from cancer (HR=0.72) and diabetes (HR=0.74). Furthermore, K2 was the only haplogroup in which mortality was reduced for all three of these common causes of death.
Seasonal Changes in Diet and Toxicity in the Climbing Mantella Frog (Mantella Laevigata)
Authors: Moskowitz Nora A. , Roland Alexandre B. , Fischer Eva K. , Ranaivorazo Ndimbintsoa , Vidoudez Charles , Aguilar Marianne T. , Caldera Sophia M. , Chea Jacqueline , Cristus Miruna G. , Crowdis Jett P. , DeMessie Bluyé , desJardins-Park Caroline R. , Effenberger Audrey H. , Flores Felipe , Giles Michael , He Emma Y. , Izmaylov Nike S. , Lee ChangWon C. , Pagel Nicholas A. , Phu Krystal K. , Rosen Leah U. , Seda Danielle A. , Shen Yong , Vargas Santiago , Murray Andrew W. , Abebe Eden , Trauger Sunia A. , Donoso David A. , Vences Miguel , O’Connell Lauren A.
Published: July 2018

Poison frogs acquire chemical defenses from the environment for protection against potential predators. These defensive chemicals are lipophilic alkaloid toxins that are sequestered by poison frogs from dietary arthropods and stored in skin glands. Despite decades of research focusing on identifying poison frog toxins, we know relatively little about how environmental variation and subsequent arthropod availability impacts toxicity in poison frogs. We investigated how seasonal environmental variation influences poison frog toxin profiles through changes in the diet of the Climbing Mantella (Mantella laevigata). We collected M. laevigata females on the Nosy Mangabe island reserve in Madagascar during the wet and dry seasons and tested the hypothesis that seasonal differences in rainfall is associated with changes in the diet and skin toxin profiles of M. laevigata. The arthropod diet of each frog was characterized into five groups (i.e. ants, termites, mites, insect larvae, or ‘other’) using visual identification and cytochrome oxidase 1 DNA barcoding. We found that frog diet differed between the wet and dry seasons, where frogs had a more diverse diet in the wet season and consumed a higher percentage of ants in the dry season. To determine if seasonality was associated with variation in frog defensive chemical composition, we used gas chromatography / mass spectrometry to quantify toxins from individual skin samples. Although the assortment of identified toxins was similar across seasons, we detected significant differences in the abundance of certain alkaloids, which we hypothesize reflects seasonal variation in the diet of M. laevigata. We suggest that these variations could originate from seasonal changes in either arthropod leaf litter composition or changes in frog behavioral patterns. Although additional studies are needed to understand the consequences of long-term environmental shifts, this work suggests that toxin profiles are relatively robust against short-term environmental perturbations.
Decreased IgG core fucosylation, a player in antibody-dependent cell-mediated cytotoxicity, is associated with autoimmune thyroid diseases
Authors: Martin Tiphaine C. , Šimurina Mirna , Ząbczyńska Marta , Kavur Marina Martinić , Rydlewska Magdalena , Pezer Marija , Kozłowska Kamila , Burri Andrea , Vilaj Marija , Turek-Jabrocka Renata , Krnjajić-Tadijanović Milena , Trofimiuk-Müldner Małgorzata , Lityńska Anna , Hubalewska-Dydejczyk Alicja , Trbojević-Akmačić Irena , Lim Ee Mun , Walsh John P. , Pochec Ewa , Spector Tim D. , Wilson Scott G. , Lauc Gordan
Published: July 2018

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins (Igs) and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells (PBMCs) glycosylation with AITD and the influence of genetic background. The study revealed an inverse association of IgG core fucosylation with TPOAb and PBMCs antennary α1,2 fucosylation with AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity (ADCC) associated with TPOAb levels.
Sequencing of Panax notoginseng genome reveals genes involved in disease resistance and ginsenoside biosynthesis
Authors: Fan Guangyi , Fu Yuanyuan , Yang Binrui , Liu Minghua , Zhang He , Liang Xinming , Shi Chengcheng , Ma Kailong , Wang Jiahao , Liu Weiqing , Shao Libin , Huang Chen , Guo Min , Cai Jing , Wong Andrew KC , Li Cheuk-Wing , Zhuang Dennis , Chen Ke-Ji , Cong Wei-Hong , Sun Xiao , Chen Wenbin , Xu Xun , Tsui Stephen Kwok-Wing , Liu Xin , Lee Simon Ming-Yuen
Published: July 2018

Panax notoginseng is a traditional Chinese herb with high medicinal and economic value. There has been considerable research on the pharmacological activities of ginsenosides contained in Panax spp.; however, very little is known about the ginsenoside biosynthetic pathway. We reported the first de novo genome of 2.36 Gb of sequences from P. notoginseng with 35,451 protein-encoding genes. Compared to other plants, we found notable gene family contraction of disease-resistance genes in P. notoginseng, but notable expansion for several ATP-binding cassette (ABC) transporter subfamilies, such as the Gpdr subfamily, indicating that ABCs might be an additional mechanism for the plant to cope with biotic stress. Combining eight transcriptomes of roots and aerial parts, we identified several key genes, their transcription factor binding sites and all their family members involved in the synthesis pathway of ginsenosides in P. notoginseng, including dammarenediol synthase, CYP716 and UGT71. The complete genome analysis of P. notoginseng, the first in genus Panax, will serve as an important reference sequence for improving breeding and cultivation of this important nutraceutical and medicinal but vulnerable plant species.
FSTbetween Archaic and Present-Day Samples
Authors: Vecchyo Diego Ortega-Del , Slatkin Montgomery
Published: July 2018

The increasing abundance of DNA sequences obtained from fossils calls for new population genetics theory that takes account of both the temporal and spatial separation of samples. Here we exploit the relationship between Wright’sFSTand average coalescence times to develop an analytic theory describing howFSTdepends on both the distance and time separating pairs of sampled genomes. We apply this theory to several simple models of population history. If there is a time series of samples, partial population replacement creates a discontinuity in pairwiseFSTvalues. The magnitude of the discontinuity depends on the extent of replacement. In stepping-stone models, pairwiseFSTvalues between archaic and present-day samples reflect both the spatial and temporal separation. At long distances, an isolation by distance pattern dominates. At short distances, the time separation dominates. Analytic predictions fit patterns generated by simulations. We illustrate our results with applications to archaic samples from European human populations. We compare present-day samples with a pair of archaic samples taken before and after a replacement event.
Gorilla APOBEC3 restricts SIVcpz and influences lentiviral evolution in great ape cross-species transmissions
Authors: Nakano Yusuke , Yamamoto Keisuke , Soper Andrew , Kumata Ryuichi , Aso Hirofumi , Misawa Naoko , Konno Yoriyuki , Kimura Izumi , Nagaoka Shumpei , Juarez-Fernandez Guillermo , Ito Jumpei , Ikeda Terumasa , Koyanagi Yoshio , Harris Reuben S , Sato Kei
Published: July 2018

Restriction factors including APOBEC3 family proteins have the potential prevent cross-species lentivirus transmissions. Such events as well as ensuing pathogenesis require the viral Vif protein to overcome/neutralize/degrade the APOBEC3 enzymes of the new host species. Previous investigations have focused on the molecular interaction between human APOBEC3s and HIV-1 Vif. However, the evolutionary interplay between lentiviruses and great ape (including human, chimpanzee and gorilla) APOBEC3s has not been fully investigated. Here we demonstrate that gorilla APOBEC3G plays a pivotal role in restricting lentiviral transmission from chimpanzee to gorilla. We also reveal that a sole amino acid substitution in Vif is sufficient to overcome the gorilla APOBEC3G-mediated species barrier. Moreover, the antiviral effects of gorilla APOBEC3D and APOBEC3F are considerably weaker than those of human and chimpanzee counterparts, which can result in the skewed evolution of great ape lentiviruses leading to HIV-1.

Highlights

SIVcpz requires M16E mutation in Vif to counteract gorilla A3G

Acidic residue at position 16 of Vif is crucial to counteract gorilla A3G

Gorilla A3D and A3F poorly suppress lentiviral infectivity

SIVgor and related HIV-1s counteract human A3D and A3F independently of DRMR motif
Predicting Functional Associations using Flanking Genes (FlaGs)
Authors: Saha Chayan Kumar , Pires Rodrigo Sanches , Brolin Harald , Delannoy Maxence , Atkinson Gemma Catherine
Published: July 2018

Analysis of conservation of gene neighbourhoods over different evolutionary levels is important for understanding operon and gene cluster evolution, and predicting functional associations. Our tool FlaGs (Flanking Genes) takes a list of NCBI protein accessions as in input, clusters neighbourhood-encoded proteins into homologous groups using sensitive sequence searching, and outputs a graphical visualization of the gene neighbourhood and its conservation, along with a phylogenetic tree annotated with flanking gene conservation. FlaGs has demonstrated utility for molecular evolutionary analysis, having uncovered a new toxin-antitoxin system in prokaryotes and bacteriophages. FlaGs can be downloaded from https://github.com/GCA-VH-lab/FlaGs or run at www.webflags.se.
ClinPhen extracts and prioritizes patient phenotypes directly from medical records to accelerate genetic disease diagnosis
Authors: Deisseroth Cole A. , Birgmeier Johannes , Bodle Ethan E. , Bernstein Jonathan A. , Bejerano Gill
Published: July 2018

Purpose

Severe genetic diseases affect 7 million births per year, worldwide. Diagnosing these diseases is necessary for optimal care, but it can involve the manual evaluation of hundreds of genetic variants per case, with many variants taking an hour to evaluate. Automatic gene-ranking approaches shorten this process by reporting which of the genes containing variants are most likely to be causing the patient’s symptoms. To use these tools, busy clinicians must manually encode patient phenotypes, which is a cumbersome and imprecise process. With 60 million patients expected to be sequenced in the next 7 years, a fast alternative to manual phenotype extraction from the clinical notes in patients’ medical records will become necessary.

Methods

We introduce ClinPhen: a fast, high-accuracy tool that automatically converts the clinical notes into a prioritized list of patient symptoms using HPO terms.

Results

ClinPhen shows superior accuracy to existing phenotype extractors, and when paired with a gene-ranking tool it significantly improve the latter’s performance.

Conclusion

Compared to manual phenotype extraction, ClinPhen saves more than 5 hours per case in Mendelian diagnosis alone. Summing over millions of forthcoming cases whose medical notes await phenotype encoding, ClinPhen makes a substantial contribution towards ending all patients’ diagnostic odyssey.
Role ofCnot6lin maternal mRNA turnover
Authors: Horvat Filip , Fulka Helena , Jankele Radek , Malik Radek , Jun Ma , Solcova Katerina , Sedlacek Radislav , Vlahovicek Kristian , Schultz Richard M. , Svoboda Petr
Published: July 2018

Removal of poly(A) tail is an important mechanism controlling eukaryotic mRNA turnover. The major eukaryotic deadenylase complex CCR4-NOT contains two deadenylase components, CCR4 and CAF1 for which mammalian CCR4 is encoded byCnot6orCnot6lparalogs. We show thatCnot6lapparently supplies the majority of CCR4 in the maternal CCR4-NOT complex in mouse, hamster, and bovine oocytes. Deletion ofCnot6lyielded viable mice butCnot6l-/-females exhibited ~40% smaller litter size. The main onset of the phenotype was post-zygotic: fertilizedCnot6l-/-eggs developed slower and arrested more frequently thanCnot6l+/-eggs suggesting that maternal CNOT6L is necessary for accurate oocyte-to-embryo transition (OET). Transcriptome analysis revealed major transcriptome changes inCnot6l-/-ovulated eggs and 1-cell zygotes. In contrast, minimal transcriptome changes in preovulatoryCnot6l-/-oocytes were consistent with reportedCnot6lmRNA dormancy. A minimal overlap between transcripts sensitive to decapping inhibition andCnot6lloss suggests that decapping and CNOT6L-mediated deadenylation selectively target distinct subsets of mRNAs during OET in mouse.
Homeostatic plasticity and external input shape neural network dynamics
Authors: Zierenberg Johannes , Wilting Jens , Priesemann Viola
Published: July 2018

In vitroandin vivospiking activity clearly differ. Whereas networksin vitrodevelop strong bursts separated by periods of very little spiking activity,in vivocortical networks show continuous activity. This is puzzling considering that both networks presumably share similar single-neuron dynamics and plasticity rules. We propose that the defining difference betweenin vitroandin vivodynamics is the strength of external input.In vitro, networks are virtually isolated, whereasin vivoevery brain area receives continuous input. We analyze a model of spiking neurons in which the input strength, mediated by spike rate homeostasis, determines the characteristics of the dynamical state. In more detail, our analytical and numerical results on various network topologies show consistently that under increasing input, homeostatic plasticity generates distinct dynamic states, from bursting, to close-to-critical, reverberating and irregular states. This implies that the dynamic state of a neural network is not fixed but can readily adapt to the input strengths. Indeed, our results match experimental spike recordingsin vitroandin vivo: thein vitrobursting behavior is consistent with a state generated by very low network input (< 0.1%), whereasin vivoactivity suggests that on the order of 1% recorded spikes are input-driven, resulting in reverberating dynamics. Importantly, this predicts that one can abolish the ubiquitous bursts ofin vitropreparations, and instead impose dynamics comparable toin vivoactivity by exposing the system to weak long-term stimulation, thereby opening new paths to establish anin vivo-like assayin vitrofor basic as well as neurological studies.
Modulatory effect of Syzygium aromaticum and Pelargonium graveolens on oxidative stress and inflammation
Authors: Marmouzi Ilias , Karym El Mostafa , Alami Rachid , Jemli Meryem El , Kharbach Mourad , Mamouch Fouzia , Faridi Bouchra , Attar Aisha , Cherrah Yahia , Faouzi My El Abbes
Published: July 2018

Background

Therapy combination is defined as disease treatment with two or more medication to acheive efficacy with lower doses or lower toxicity. Regarding its reported toxicities and efficacy, the Essential Oils (EOs) from Syzygium aromaticum (SA) and Pelargonium graveolens (PG) were combined for in vitro and in vivo assays and toxicities.

Methods

The Essential Oils and mixture were tested for in vivo/in vitro antioxidant and anti-inflammatory activities. The assays included the animal model of acute inflammation (carrageenan model), the protective effect on H2O2/Sodium nitroprissude induced stress in Tetrahymena pyriformis, and the in vitro antioxidant assays.

Results

The chemical analysis of the investigated Oils has lead to the identification of Eugenol (74.06%), Caryophyllene (11.52%) and Carvacrol acetate (7.82%) as the major element in SA; while PG was much higher in Citronellol (30.77%), 10-epi-γ-Eudesmol (22.59%), and Geraniol (13.95%). In our pharmacological screening of samples, both Oils demonstrated good antioxidant effects. In vivo investigation of the antioxidant activity in the protozoa model (T. pyriformis) demonstrated a lesser toxic effect of EOs mixture with no significant differences when oxidative stress markers and antioxidant enzymes (MDA, SOD and CAT) were evaluated. On the other hand the in vivo model of inflammatory response to carrageenan demonstrated a good inhibitory potential of both EOs. The EOs Mixture demonstrated equivalent bioactivity with lower toxic effect and minimal risk for each compound.

Conclusions

The results from this study indicate that EOs mixture from SA and PG demonstrated promising modulatory antioxidant/anti-inflammatory effect, which suggest an efficient association for therapy.
Super-resolution fight club: A broad assessment of 2D & 3D single-molecule localization microscopy software
Authors: Sage Daniel , Pham Thanh-An , Babcock Hazen , Lukes Tomas , Pengo Thomas , Chao Jerry , Velmurugan Ramraj , Herbert Alex , Agrawal Anurag , Colabrese Silvia , Wheeler Ann , Archetti Anna , Rieger Bernd , Ober Raimund , Hagen Guy M. , Sibarita Jean-Baptiste , Ries Jonas , Henriques Ricardo , Unser Michael , Holden Seamus
Published: July 2018

With the widespread uptake of 2D and 3D single molecule localization microscopy, a large set of different data analysis packages have been developed to generate super-resolution images. To guide researchers on the optimal analytical software for their experiments, we have designed, in a large community effort, a competition to extensively characterise and rank these options. We generated realistic simulated datasets for popular imaging modalities – 2D, astigmatic 3D, biplane 3D, and double helix 3D – and evaluated 36 participant packages against these data. This provides the first broad assessment of 3D single molecule localization microscopy software, provides a holistic view of how the latest 2D and 3D single molecule localization software perform in realistic conditions, and ultimately provides insight into the current limits of the field.
Super-Mendelian inheritance mediated by CRISPR/Cas9 in the female mouse germline
Authors: Grunwald Hannah A. , Gantz Valentino M. , Poplawski Gunnar , Xu Xiang-ru S. , Bier Ethan , Cooper Kimberly L.
Published: July 2018

A gene drive biases the transmission of a particular allele of a gene such that it is inherited at a greater frequency than by random assortment. Recently, a highly efficient gene drive was developed in insects, which leverages the sequence-targeted DNA cleavage activity of CRISPR/Cas9 and endogenous homology directed repair mechanisms to convert heterozygous genotypes to homozygosity. If implemented in laboratory rodents, this powerful system would enable the rapid assembly of genotypes that involve multiple genes (e.g., to model multigenic human diseases). Such complex genetic models are currently precluded by time, cost, and a requirement for a large number of animals to obtain a few individuals of the desired genotype. However, the efficiency of a CRISPR/Cas9 gene drive system in mammals has not yet been determined. Here, we utilize an active genetic “CopyCat” element embedded in the mouse Tyrosinase gene to detect genotype conversions after Cas9 activity in the embryo and in the germline. Although Cas9 efficiently induces double strand DNA breaks in the early embryo and is therefore highly mutagenic, these breaks are not resolved by homology directed repair. However, when Cas9 expression is limited to the developing female germline, resulting double strand breaks are resolved by homology directed repair that copies the CopyCat allele from the donor to the receiver chromosome and leads to its super-Mendelian inheritance. These results demonstrate that the CRISPR/Cas9 gene drive mechanism can be implemented to simplify complex genetic crosses in laboratory mice and also contribute valuable data to the ongoing debate about applications to combat invasive rodent populations in island communities.
What you see depends on what you hear: temporal averaging and crossmodal integration
Authors: Chen Lihan , Zhou Xiaolin , Müller Hermann J. , Shi Zhuanghua
Published: July 2018

In our multisensory world, we often rely more on auditory information than on visual input for temporal processing. One typical demonstration of this is that the rate of auditory flutter assimilates the rate of concurrent visual flicker. To date, however, this auditory dominance effect has largely been studied using regular auditory rhythms. It thus remains unclear whether irregular rhythms would have a similar impact on visual temporal processing; what information is extracted from the auditory sequence that comes to influence visual timing; and how the auditory and visual temporal rates are integrated together in quantitative terms. We investigated these questions by assessing, and modeling, the influence of a task-irrelevant auditory sequence on the type of ‘Ternus apparent motion’: group motion versus element motion. The type of motion seen critically depends on the time interval between the two Ternus display frames. We found that an irrelevant auditory sequence preceding the Ternus display modulates the visual interval, making observers perceive either more group motion or more element motion. This biasing effect manifests whether the auditory sequence is regular or irregular, and it is based on a summary statistic extracted from the sequential intervals: their geometric mean. However, the audiovisual interaction depends on the discrepancy between the mean auditory and visual intervals: if it becomes too large, no interaction occurs – which can be quantitatively described by a partial Bayesian integration model. Overall, our findings reveal a crossmodal perceptual averaging principle that may underlie complex audiovisual interactions in many everyday dynamic situations.

Public Significance Statement

The present study shows that auditory rhythms, regardless of their regularity, can influence the way in which the visual system times (subsequently presented) events, thereby altering dynamic visual (motion) perception. This audiovisual temporal interaction is based on a summary statistic derived from the auditory sequence: the geometric mean interval, which is then combined with the visual interval in a process of partial Bayesian integration (where integration is unlikely to occur if the discrepancy between the auditory and visual intervals is too large). We propose that this crossmodal perceptual averaging principle underlies complex audiovisual interactions in many everyday dynamic perception scenarios.

Author Note

This study was supported by grants from the Natural Science Foundation of China (31200760, 61621136008, 61527804), German DFG project SH166 3/1 and “projektbezogener Wissenschaftleraustausch” (proWA). The data, and the source code of statistical analysis and modeling are available at https://github.com/msenselab/temporal_averaging. Part of the study has been presented as a talk in 17th International Multisensory Research Forum (IMRF, June 2016, Suzhou, China).
Going beyond western dualism: towards corporate nature responsibility reporting
Authors: Gallhofer Sonja
Published: July 2018

Purpose

The purpose of this paper is to outline an ecofeminist lens for the analysis of accounting, which is applied to: first, the critique of corporate social responsibility reporting (CSRR); second, the elaboration of elements of a framework for a new accounting – corporate nature responsibility reporting (CNRR) – as a response to the critique of CSRR; and, third, the consideration of elements of an enabling and emancipatory praxis in the context of CNRR, including a sketch of a research agenda.

Design/methodology/approach

The paper presents a critical application of aspects of the ecofeminist critique of Western dualism and its emphasis on wholeness, interconnectedness and relatedness, including its particular delineation of nature, to the critique and design of accounting.

Findings

Insights from the application of an ecofeminist lens to the critique of CSRR raise questions about the suitability of the western notion of corporate social responsibility (CSR) and its associated accounting currently in use. In order to go beyond critique, the paper introduces the notions of corporate nature responsibility (CNR) and CNRR and offers an outline of key elements of CNRR and an emancipatory praxis in the context of CNRR, including a sketch of a research agenda. The author’s elaborations suggest that in order to overcome the limitations of CSR and CSRR, a corporation ought to be concerned about its broader and holistic CNR. And, it should provide a CNR report, as part of a holistic CNRR concerned with the performance of the company in the context of CNR.

Social implications

Through creating new visibilities, CNRR has the potential to enhance the well-being of people and nature more generally.

Originality/value

Ecofeminism’s critique of western dichotomous thinking has been given little consideration in prior studies of accounting. The paper thus draws attention to the relevance of an ecofeminist theoretical lens for the critique and design of accounting by focussing on CSRR. The paper introduces the concepts of CNR and CNRR to address the limitations of CSRR as currently practiced.
Urban Indian adolescents practise unhealthy dietary behaviours
Authors: Rathi Neha , Riddell Lynn , Worsley Anthony
Published: July 2018

Purpose

The rising prevalence of obesity among Indian adolescents has underscored the need to develop effective strategies to reduce this epidemic. The purpose of this paper is to assess the patterns of snacking, meal consumption and fast food consumption among adolescents in private schools in Kolkata, India.

Design/methodology/approach

A cross-sectional, paper-based, self-administered dietary and lifestyle survey was completed by 1,026 year-nine students aged 14–16 years. Cross-tabulation analyses were performed to compare the frequencies of various dietary behaviours across gender.

Findings

The two most common episodes for snacking among respondents were while watching television (57.9 per cent) and while interacting with peers (54.1 per cent). In contrast, snacking throughout the day (8.7 per cent) and in the middle of the night (7.8 per cent) were minimally practiced by the adolescents. The most regularly consumed meal was lunch (94.6 per cent), whereas the most frequently missed meal was breakfast (14.0 per cent). Fast food was most frequently consumed as snacks (26.8 per cent) but least frequently consumed for lunch (9.2 per cent). Overall, boys exhibited more unhealthy dietary behaviours than girls.

Practical implications

These findings highlight the need to develop nutrition education programmes for nutritionally vulnerable adolescents which communicate the importance of regular meal consumption, reduced intake of fast food and less snacking on energy-dense, nutrient-poor foods.

Originality/value

This is the first cross-sectional survey to investigate patterns of snacking, meal consumption and fast food consumption amongst urban Indian adolescents.
Relational capital and knowledge transfer in universities
Authors: Paoloni Paola , Cesaroni Francesca Maria , Demartini Paola
Published: July 2018

Purpose

The importance of relational capital for the university has grown enormously in recent years. In fact, relational capital allows universities to promote and emphasize the effectiveness of the third mission. The purpose of this paper is to propose a case study involving an Italian university that recently set up a new research observatory, and, thanks to its success, succeeded in enhancing its relational capital.

Design/methodology/approach

The authors adopted an action research approach to analyze the case study. Consistently, the authors followed the analysis, diagnosis, and intervention phases. First, the authors focused on the identification of the strengths and weaknesses of the process through which the university created relational capital, and finally, the authors proposed solutions to improve the process.

Findings

This case study shows that the creation of relation capital for the host university was the result of a process of transfer and transformation of the individual relationships of the observatory’s promoters.

Originality/value

This paper contributes to filling a significant gap in the literature on relational capital and universities and provides useful insights into how these organizations can encourage its creation. It also allows scholars, managers, and politicians involved in higher education to gain a greater understanding of this relevant topic.
Do Millennials prefer to be shown appreciation differently?
Authors: White Paul
Published: July 2018

Purpose

Research demonstrates that feeling appreciated in the workplace increases employee engagement, reduces turnover, and increases profitability. Despite the fact that people differ in how they feel most appreciated, no work to date has explored the impact of age differences on appreciation preferences. The purpose of this paper is to determine if Millennial workers vs their older colleagues differ in the manner they prefer to be shown appreciation.

Design/methodology/approach

From 2014 to 2018, 62,156 workers completed the Motivating by Appreciation Inventory (White, 2011) and provided age, gender, and work industry information. Each person’s primary and the least valued languages of appreciation in the workplace were identified. Four age groups were created of approximately equal numbers: ≤29-, 30-39-, 40-49-, and 50+ years old.

Findings

Words of Affirmation was the most prominent primary language of appreciation across all four age groups and most pronounced in the oldest group (50+). The ≤29-year-old group valued Quality Time more and Acts of Service less than the other three age groups. There were no age group differences in the least valued language of appreciation.

Practical implications

The results suggest that supervisors and staff members must be mindful to include opportunities for quality time interactions with Millennial workers, as well as provide words of affirmation, to show appreciation for their work.

Originality/value

This is the first study to assess age differences in preferred ways to be shown appreciation in the workplace.
Development of bansho (board writing) analysis as a research method to improve observation and analysis of instruction in lesson study
Authors: Tan Shirley , Fukaya Kumi , Nozaki Shiho
Published: July 2018

Purpose

The purpose of this paper is to develop bansho analysis as a research method to improve observation and analysis of instruction in lesson study, which could potentially visualise pupils’ thinking processes in a lesson.

Design/methodology/approach

The paper opted for a qualitative method of case study analysis. Data are drawn from a Year 6 Japanese Language lesson of a Japanese primary school. Data collection and data analysis are informed by transcript-based lesson analysis. The process of bansho formation is also reproduced based on video and audio data.

Findings

Bansho analysis illustrates three main patterns of pupils’ thinking processes, namely, variation of ideas, connection of ideas and attention to ideas. Pupils’ opinion sharing at the beginning of the lesson led to a variety of ideas and they were recorded as part of bansho. There, pupils proceeded to establish connection among ideas. Finally, pupils displayed attention to ideas which were recorded on bansho, by returning to ideas that intrigued them.

Research limitations/implications

There is a need to investigate the teacher’s role in bansho formation processes in order to develop a more comprehensive bansho analysis method. Other teaching and learning materials such as lesson plans and pupils’ notes should also be included in the study of bansho to develop a more comprehensive bansho analysis.

Originality/value

Bansho analysis proposed in this paper allows educators and researchers to study bansho with visualisation of bansho-related data. It would serve as an invaluable source of evidence during the observation and reflection stage of lesson study cycle.
Analysing the object of learning, using phenomenography
Authors: Ahlstrand Pernilla
Published: July 2018

Purpose

In this paper, knowledge concerning the meaning of knowing the object of learning is developed using learning study as a research approach. The purpose of this paper is to show how the object of learning, in this case, playing with groove in rhythmic sequences, can be analysed and recognised using phenomenography.

Design/methodology/approach

The paper reports on a learning study conducted in three different fifth grade elementary school classes. Seven music teachers were involved in preparing the pre-test, designing three research lessons and analysing the material.

Findings

The findings show that several aspects of the object of learning must be discerned by the learner in order to experience the chosen object of learning and develop in the learning situation. The phenomenographic analysis contributed to refining the meaning of the object of learning.

Originality/value

In a learning study, knowledge concerning the meaning of the object of learning is generated. The development and specification of this knowledge will be empirically revealed through the analysis process. This paper will contribute to the discussion concerning what must be known in order to develop a specific capability in music education, namely, the capability to feel the groove.