bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of Static and Dynamic Network Metrics in the Resting-State: A MEG-beamformed Connectivity Analysis
Authors: Dimitriadis S. I. , Routley B. , Linden D. , Singh K.D.
Published: June 2018

The resting activity of the brain can be described by so-called intrinsic connectivity networks (ICNs), which consist of spatially and temporally distributed, but functionally connected, nodes. The coordinated activity of the resting state can be explored via magnetoencephalography (MEG) by studying frequency-dependent functional brain networks at the source level. Although many algorithms for the analysis of brain connectivity have been proposed, the reliability of network metrics derived from both static and dynamic functional connectivity is still unknown. This is a particular problem for studies of associations between ICN metrics and personality variables or other traits, and for studies of differences between patient and control groups, which both depend critically on the reliability of the metrics used. A detailed investigation of the reliability of metrics derived from resting-state MEG repeat scans is therefore a prerequisite for the development of connectomic biomarkers.

Here, we first estimated both static (SFC) and dynamic functional connectivity (DFC) after beamforming source reconstruction using the imaginary part of the phase locking index (iPLV) and the correlation of the amplitude envelope (CorEnv). Using our approach, functional network microstates (FCμstates) were derived from the DFC and chronnectomics were computed from the evolution of FCμstates across experimental time. In both temporal scales, the reliability of network metrics (SFC), the FCμstates and the related chronnectomics were evaluated for every frequency band.

Chronnectomic parameters and FCμstates were generally more reliable than node-wise static network metrics. CorEnv-based network metrics were more reproducible at the static approach. This analysis encourages the analysis of MEG resting-state via DFC.
Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age
Authors: Seaman Kendra L. , Smith Christopher T. , Juarez Eric J. , Dang Linh C. , Castrellon Jaime J. , Burgess Leah L. , Danica San Juan M. , Kundzicz Paul M. , Cowan Ronald L. , Zald David H. , Samanez-Larkin Gregory R.
Published: June 2018

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age-related change in function across cortical and subcortical sub-regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross-sectional adult age differences in estimates of D2-like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [18F]fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (∼6–16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (∼3–5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (∼0–2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.
Imputation of Behavioral Candidate Gene Repeat Polymorphisms in 486,551 Publicly-Available UK Biobank Individuals
Authors: Border Richard , Smolen Andrew , Corley Robin P. , Stallings Michael C. , Brown Sandra A. , Conger Rand D. , Derringer Jaime , Donnellan M. Brent , Haberstick Brett C. , Hewitt John K. , Hopfer Christian , Krauter Ken , McQueen Matthew B. , Wall Tamara L. , Keller Matthew C. , Evans Luke M.
Published: June 2018

Some of the most widely studied polymorphisms in psychiatric genetics include variable number tandem repeat polymorphisms (VNTRs) in SLC6A3, DRD4, SLC6A4, and MAOA. While initial findings suggested large effects, their importance with respect to psychiatric phenotypes is the subject of much debate with broadly conflicting results. Despite broad interest, these loci remain absent from the largest available samples, such as the UK Biobank, limiting researchers’ ability to test these contentious hypotheses rigorously in large samples. Here, using two independent reference datasets, we report out-of-sample imputation accuracy estimates of >0.96 for all four VNTR polymorphisms and one modifying SNP, depending on the reference and target dataset. We describe the imputation procedures of these candidate polymorphisms in 486,551 UK Biobank individuals, and have made the imputed polymorphism data available to UK Biobank researchers. This resource, provided to the community, will allow the most rigorous tests to-date of the roles of these polymorphisms in behavioral and psychiatric phenotypes.
Fast and Robust Deconvolution of Tumor Infiltrating Lymphocyte from Expression Profiles using Least Trimmed Squares
Authors: Hao Yuning , Yan Ming , Lei Yu L. , Xie Yuying
Published: June 2018

Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative to develop a robust deconvolution method that automatically decontaminates data by reliably detecting and removing outliers. We developed a new machine learning tool, Fast And Robust DEconvolution of Expression Profiles (FARDEEP), to enumerate immune cell subsets from whole tumor tissue samples. To reduce noise in the tumor gene expression datasets, FARDEEP utilizes an adaptive least trimmed square to automatically detect and remove outliers before estimating the cell compositions. We show that FARDEEP is less susceptible to outliers and returns a better estimation of coefficients than the existing methods with both numerical simulations and real datasets. FARDEEP provides the absolute quantitation of each immune cell subset in addition to relative percentages. Hence, FARDEEP represents a novel robust algorithm to complement the existing toolkit for the characterization of tissue-infiltrating immune cell landscape. The source code for FARDEEP as implemented in R is available for download at https://goo.gl/SqGKuo.
Microbial coexistence through chemical-mediated interactions
Authors: Niehaus Lori , Boland Ian , Liu Minghao , Chen Kevin , Fu David , Henckel Catherine , Chaung Kaitlin , Miranda Suyen Espinoza , Dyckman Samantha , Crum Matthew , Dedrick Sandra , Shou Wenying , Momeni Babak
Published: June 2018

Many microbial functions happen within communities of interacting species. Explaining how species with intrinsically disparate fitness can coexist is important for applications such as manipulating host-associated microbiota or engineering industrial communities. Previous coexistence studies have often neglected interaction mechanisms. Here, we formulate and experimentally constrain a model in which chemical mediators of microbial interactions (e.g. metabolites or waste-products) are explicitly incorporated. We construct many instances of coexistence by simulating community assembly through enrichment and ask how species interactions can explain coexistence. We show that growth-facilitating influences between members are favored in assembled communities. Among negative influences, self-restraint, such as production of self-inhibiting waste, contributes to coexistence, whereas inhibition of other species disrupts coexistence. Coexistence is also favored when interactions are mediated bydepletablechemicals that get consumed or degraded, rather than byreusablechemicals that are unaffected by recipients. Our model creates null predictions for coexistence driven by chemical-mediated interactions.
Multimodal music perception engages motor prediction: a TMS study
Authors: Gordon Chelsea L. , Iacoboni Marco , Balasubramaniam Ramesh
Published: June 2018

Cortico-spinal excitability (CSE) in humans measured with Transcranial Magnetic Stimulation (TMS) is generally increased by the perception of other people’s actions. This perception can be unimodal (visual or auditory) or multimodal (visual and auditory). The increase in TMS-measured CSE is typically prominent for muscles involved in the perceived action (muscle specificity). There are two main classes of accounts for this phenomenon. One suggests that the motor system mirrors the actions that the observer perceives (the resonance account). The other suggests that the motor system predicts the actions that the observer perceives (the predictive account). To test these accounts (which need not be mutually exclusive), subjects were presented with four versions of three-note piano sequences: sound only, sight only, audiovisual, and audiovisual with sound lagging behind while CSE was measured in two hand muscles. Muscle specificity did not interact with modality in the flexor digiti minimi (FDM), but was reliably higher for the first dorsal interosseous (FDI) while subjects perceived the audiovisual version of the three-note piano sequences with sound lagging behind. Since this version of the three-note piano sequences is the only one that overtly violates experience-based expectations, this finding supports predictive coding accounts of motor facilitation during action perception.
Gene activation precedes DNA demethylation in response to infection in human dendritic cells
Authors: Pacis Alain , Mailhot-Léonard Florence , Tailleux Ludovic , Randolph Haley E , Yotova Vania , Dumaine Anne , Grenier Jean-Christophe , Barreiro Luis B
Published: June 2018

DNA methylation is considered to be a relatively stable epigenetic mark. Yet, a growing body of evidence indicates that DNA methylation levels can change rapidly, for example, in innate immune cells facing an infectious agent. Nevertheless, the causal relationship between changes in DNA methylation and gene expression during infection remains to be elucidated. Here, we generated time-course data on DNA methylation, gene expression, and chromatin accessibility patterns during infection of human dendritic cells with Mycobacterium tuberculosis. We found that the immune response to infection is accompanied by active demethylation of thousands of CpG sites overlapping distal enhancer elements. However, virtually all changes in gene expression in response to infection occur prior to detectable changes in DNA methylation, indicating that the observed losses in methylation are a downstream consequence of transcriptional activation. Footprinting analysis revealed that immune-related transcription factors (TF), such as NF-κB/Rel, are recruited to enhancer elements prior to the observed losses in methylation, suggesting that DNA demethylation is mediated by TF binding to cis-acting elements. Collectively, our results show that DNA demethylation is not required for the establishment of the core regulatory program engaged upon infection.
Robust and stable transcriptional repression inGiardiausing CRISPRi
Authors: McInally SG , Hagen KD , Nosala C , Williams J , Nguyen K , Booker J , Jones K , Scott C. Dawson
Published: June 2018

Giardia lambliais a binucleate protistan parasite causing significant diarrheal disease worldwide. An inability to target Cas9 to both nuclei, combined with the lack of non-homologous end joining and markers for positive selection, has stalled the adaptation of CRISPR/Cas9-mediated genetic tools for this widespread parasite. CRISPR interference (CRISPRi) is a modification of the CRISPR/Cas9 system that directs catalytically inactive Cas9 (dCas9) to target loci for stable transcriptional repression. Using aGiardianuclear localization signal to target dCas9 to both nuclei, we developed efficient and stable CRISPRi-mediated transcriptional repression of exogenous and endogenous genes inGiardia. Specifically, CRISPRi knockdown of kinesin-2a and kinesin-13 causes severe flagellar length defects that mirror defects with morpholino knockdown. Knockdown of the ventral disc MBP protein also causes severe structural defects that are highly prevalent and persist in the population more than five days longer than transient morpholino-based knockdown. By expressing two gRNAs in tandem to simultaneously knock down kinesin-13 and MBP, we created a stable dual knockdown strain with both flagellar length and disc defects. The efficiency and simplicity of CRISPRi in polyploidGiardiaallows for rapid evaluation of knockdown phenotypes and highlights the utility of CRISPRi for emerging model systems.
Nested oscillatory dynamics in cortical organoids model early human brain network development
Authors: Trujillo Cleber A. , Gao Richard , Negraes Priscilla D. , Chaim Isaac A. , Domissy Alain , Vandenberghe Matthieu , Devor Anna , Yeo Gene W. , Voytek Bradley , Muotri Alysson R.
Published: June 2018

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex.

HIGHLIGHTS

Early development of human functional neural networks and oscillatory activity can be modeled in vitro.

Cortical organoids exhibit phase-amplitude coupling between delta oscillation (2 Hz) and high-frequency activity (100-400 Hz) during network-synchronous events.

Differential role of glutamate and GABA in initiating and maintaining oscillatory network activity.

Developmental impairment of MECP2-KO cortical organoids impacts the emergence of oscillatory activity.

Cortical organoid network electrophysiological signatures correlate with human preterm neonatal EEG features.

eTOC

Brain oscillations are a candidate mechanism for how neural populations are temporally organized to instantiate cognition and behavior. Cortical organoids initially exhibit periodic and highly regular nested oscillatory network events that eventually transition to more spatiotemporally complex activity, capturing features of late-stage preterm infant electroencephalography. Functional neural circuitry in cortical organoids exhibits emergence and development of oscillatory network dynamics similar to those found in the developing human brain.
Coopting the Lap system ofPseudomonas fluorescensto reversibly customize bacterial cell surfaces
Authors: Smith T. Jarrod , Sondermann Holger , O’Toole George A.
Published: June 2018

Initialattachment to a surface is a key and highly regulated step in biofilm formation. In this study, we present a platform for reversibly functionalizing bacterial cell surfaces, with an emphasis on designing biofilms. We engineered the Lap system ofPseudomonas fluorescensPf0-1, which is normally used to regulate initial cell surface attachment, to display various protein cargo at the bacterial cell surface and control extracellular release of the cargo in response to changing levels of the second messenger cdi-GMP. To accomplish this goal, we fused the protein cargo between the N-terminal retention module and C-terminal secretion signal of LapA, and controlled surface localization of the cargo with natural signals known to stimulate or deplete c-di-GMP levels inP. fluorescensPf0-1. We show this system can tolerate large cargo in excess of 500 amino acids, directP. fluorescensPf0-1 to surfaces it does not typically colonize, and program this microbe to sequester the toxic medal cadmium.
Pre-stimulus oscillatory activity predicts successful episodic encoding for both young and older adults
Authors: Strunk Jon , Duarte Audrey
Published: June 2018

Healthy aging is associated with declines in episodic memory performance that are due in part to deficits in encoding. Emerging results from young adult studies suggest that the neural activity during the time-period preceding stimulus presentation is sensitive to episodic memory performance. It is unknown whether age-related declines in episodic memory are due solely to changes in the recruitment of processes elicited by stimuli during encoding or also in processes recruited in anticipation of these stimuli. Here, we recorded oscillatory EEG while young and old participants encoded visual and auditory words that were preceded by cues indicating the stimulus modality. Alpha oscillatory activity preceding and following stimulus onset was predictive of subsequent memory accuracy similarly across age. Frontal beta oscillations linked to semantic elaboration during encoding were reduced by age. Post-stimulus theta power was positively predictive of episodic memory accuracy for old but not young adults, potentially reflecting older adults’ tendency to self-generate associations during encoding. Collectively, these results suggest that the preparatory mobilization of neural processes prior to encoding that benefits episodic memory performance is not affected by age.
Adjunct phage treatment enhances the effectiveness of low antibiotic concentration againstStaphylococcus aureusbiofilmsin vitro
Authors: Dickey James , Perrot Véronique
Published: June 2018

Phage therapy is drawing more interest as antibiotic resistance becomes an ever more serious threat to public health. Bacterial biofilms represent a major obstacle in the fight against bacterial infections as they are inherently refractory to many types of antibiotics. Treating biofilms with phage has shown promise in a handful of experimental and case studies. However, quantification of the effect of phage combined with antibiotics is needed to pave the way for larger clinical trials. Here we explore the effect of using phage in combination with a total of nine antibiotics, applied simultaneously or as a pretreatment before antibiotics are applied to in vitro biofilms ofStaphylococcus aureus. Most antibiotics alone were ineffective at low concentration (2×MIC), but the addition of phage to treatment regimens led to substantial improvements in efficacy. At high concentration (10×MIC), antibiotics alone were effective, and in most cases the addition of phage to treatment regimens did not improve efficacy. Using phage with rifampin was also very effective at reducing the outgrowth of resistant strains during the course of treatment.
Peculiar features of the plastids of the colourless algaEuglena longaand photosynthetic euglenophytes unveiled by transcriptome analyses
Authors: Záhonová Kristína , Füssy Zoltán , Birčák Erik , Novák Vanclová Anna M. G. , Klimeš Vladimír , Vesteg Matej , Krajčovič Juraj , Oborník Miroslav , Eliáš Marek
Published: June 2018

Background:Euglenophytes are an interesting algal group that emerged within the ancestrally plastid-lacking Euglenozoa phylum by acquiring a plastid from a green algal donor. However, the knowledge of euglenophyte plastid biology and evolution is highly incomplete, partly because euglenophytes have so far been little studied on a genome- and transcriptome-wide scale. Transcriptome data from only a single species,Euglena gracilis, have been exploited to functional insights, but aspects of the plastid biology have been largely neglected.

Results:To expand the resources for studying euglenophyte biology and to improve our knowledge of the euglenophyte plastid function and evolution, we sequenced and analysed the transcriptome of the non-photosynthetic speciesEuglena longa. The transcriptomic data confirmed the absence of genes for the photosynthetic machinery in this species, but provided a number of candidate plastid-localized proteins bearing the same type of N-terminal bipartite topogenic signals (BTSs) as known from the photosynthetic speciesE. gracilis. Further comparative analyses using transcriptome assemblies available forE. gracilisand two additional photosynthetic euglenophytes of the genusEutreptiellaenabled us to unveil several salient aspects of the basic plastid infrastructure in euglenophytes. First, a number of plastidial proteins seem to reach the organelle as C-terminal translational fusions with other BTS-bearing proteins. Second, the conventional eubacteria-derived plastidial ribosomal protein L24 is missing and seems to have been replaced by very different homologs of the archaeo-eukaryotic origin. Third, no homologs of any key component of the TOC/TIC system (translocon of the outer/inner chloroplast membrane) and the plastid division apparatus are discernible in euglenophytes, and the machinery for intraplastidial protein targeting has been simplified by the loss of the cpSRP/cpFtsY system and the SEC2 translocon. Lastly, euglenophytes proved to encode a plastid-targeted homolog of the termination factor Rho horizontally acquired from a Lambdaproteobacteria-related donor, suggesting an unprecedented modification of the transcription mechanism in their plastid.

Conclusions:Our study suggests that the euglenophyte plastid has been substantially remodelled comparted to its green algal progenitor by both loss of original and acquisition of novel molecular components, making it a particularly interesting subject for further studies.
Seizures start as silent microseizures by neuronal ensembles
Authors: Wenzel Michael , Hamm Jordan P. , Peterka Darcy S. , Yuste Rafael MD
Published: June 2018

Understanding seizure formation and spread remains a critical goal of epilepsy research. While many studies have documented seizure spread, it remains mysterious how they start. We used fast in-vivo two-photon calcium imaging to reconstruct, at cellular resolution, the dynamics of focal cortical seizures as they emerge in epileptic foci (intrafocal), and subsequently propagate (extrafocal). We find that seizures start as intrafocal coactivation of small numbers of neurons (ensembles), which are electrographically silent. These silent “microseizures” expand saltatorily until they break into neighboring cortex, where they progress smoothly and first become detectable by LFP. Surprisingly, we find spatially heterogeneous calcium dynamics of local PV interneuron sub-populations, which rules out a simple role of inhibitory neurons during seizures. We propose a two-step model for the circuit mechanisms of focal seizures, where neuronal ensembles first generate a silent microseizure, followed by widespread neural activation in a travelling wave, which is then detected electrophysiologically.
Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth
Authors: Pereyra Silvana , Sosa Claudio , Bertoni Bernardo , Sapiro Rossana
Published: June 2018

Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results of the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proved challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. A common pathway of labor and PTB may be the activation of fetal membranes. In this work, chorioamnion membranes from severe preterm and term fetus were analyzed using RNA sequencing. A total of 270 genes were differentially expressed (DE): 252 were up-regulated and 18 were down-regulated in the severe preterm compared to the term births. We found great gene expression homogeneity in the control samples, and not in severe preterm samples. In this work, we identified up-regulated pathways that were previously suggested as leading to PTB like immunological and inflammatory paths. New pathways that were not identified in preterm like the hemopoietic path appeared up-regulated in preterm membranes. A group of 18 down-regulated genes discriminates between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the down-regulated genes are involved in the nervous system, morphogenesis (WNT-1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, KCNB1), making them good candidates as biomarkers of PTB.

The identification of this DE gene pattern may help to develop a multi-gene disease classifier. These markers were generated in an admixtured South American population where PTB has a high incidence. Since genetic background may impact differentially in different populations it is mandatory to include populations like South American and African ones that are usually excluded from high throughput approaches. These classifiers should be compared to those in other populations to get a global landscape of PTB.
Visualization of the type III secretion mediated
Salmonella
-host cell interface using cryo-electron tomography
Authors: Liu Jun , Park Donghyun , Lara-Tejero Maria , Galan Jorge E , Li Wenwei , Waxham M Neal , Hu Bo
Published: June 2018

Many important gram-negative bacterial pathogens use highly sophisticated type III secretion systems (T3SSs) to establish complex host-pathogen interactions. Bacterial-host cell contact triggers the activation of the T3SS and the subsequent insertion of a translocon pore into the target cell membrane, which serves as a conduit for the passage of effector proteins. Therefore the initial interaction between T3SS-bearing bacteria and host cells is the critical step in the deployment of the protein secretion machine, yet this process remains poorly understood. Here, we use high-throughput cryo-electron tomography (cryo-ET) to visualize the T3SS-mediated
Salmonella
-host cell interface. Our analysis reveals the intact translocon at an unprecedented level of resolution, its deployment in the host cell membrane, and the establishment of an intimate association between the bacteria and the target cells, which is essential for effector translocation. Our studies provide critical data supporting the long postulated direct injection model for effector translocation.
Visual signals suppress Alpha Power Increases & Frequency Decreases before and after a Mindfulness Meditation Intervention for Problem Gambling
Authors: Martin Kaili-Larissa , Jindani Farah , Turner Nigel , DeSouza Joseph FX
Published: June 2018

The use of mindfulness meditation (MM) in the treatment of problem gambling (PG), has been used effectively for over five years. However, the neural mechanisms responsible for the improvements are unknown. The literature describes healthy individuals with an increase in alpha power and a decrease in alpha frequency after eight weeks of mindfulness meditation, but it is unknown if changes are similar amongst individuals with PG. Using resting-state electroencephalography (rsEEG), we measured the changes in alpha oscillations before and after an eight-week mindfulness meditation intervention (MMi) and a pre/ post-five-minute mindfulness meditation body scan (MMb). For people with PG, we observed an increase in alpha power and decreased alpha peak frequency after the MMi, while the inverse was true for the MMb. The most considerable alpha rhythm changes occurred in the frontal and temporal lobes, areas sensitive to reward and sensory processing in PG. Our observed changes may reflect theories that MMi for PG may improve attentional control as hypothesized by previous research in alpha oscillations and cue-reward processing.
Neurobiological Basis of Brain Blood Oxygenation Responses Correlated with Cognitive Stroop Task Performance Before and After an Acute Bout of Aerobic Exercise
Authors: Pal Amrita
Published: June 2018

Cardiovascular activities may increase the brain blood flow improving neural activities leading to improved cognition. Consequently, the effects of an acute bout of moderate intensity aerobic exercise on cortical brain blood oxygenation and its correlation with cognitive color-word Stroop task performance were tested. The Stroop tasks were congruent (color matches word) and incongruent (color does not match word). Prefrontal (PFC) and motor cortex (MC) blood flow was recorded by fNIRS (functional Near-Infrared Spectroscopy) while the human subjects performed the Stroop tasks before and after 30 minutes of exercise or equivalent time of rest (controlling for practice effect of repeating the Stroop task multiple times). It was predicted that PFC blood flow increase after exercise will correlate with increased Stroop interference and decreased cognitive flexibility after an acute bout of aerobic exercise at 70% of maximal Heart Rate (HR). We observed that Stroop interference in aerobic exercise and practice alone (rest) were not significantly (p>0.6) different indicating that exercise did not improve cognition above the learning effect. Increase in blood flow (both neurovascular and neurometabolic coupling) in previously deactivated PFC channels was positively correlated (p<0.05) to increased Stroop interference (worse cognitive speed and accuracy) after an acute bout of aerobic exercise.

Highlights

Does moderate intensity aerobic exercise improve cognition?

Does prefrontal cortex oxygenation correlate with cognition changes after exercise?
Using LASSO in gene co-expression network for genome-wide identification of gene interactions responding to salt stress in rice
Authors: Du Qian , Campbell Malachy , Yu Huihui , Liu Kan , Walia Harkamal , Zhang Qi , Zhang Chi
Published: June 2018

In many applications, such as gene co-expression network analyses, data arises with a huge number of covariates while the size of sample is comparatively small. To improve the accuracy of prediction, variable selection is often used to get a sparse solution by forcing coefficients of variables contributing less to the observed response variable to zero. Various algorithms were developed for variable selection, but LASSO is well known for its statistical accuracy, computational feasibility and broad applicability to adaptation. In this project, we applied LASSO to the gene co-expression network of rice with salt stress to discover key gene interactions for salt-tolerance related phenotypes. The dataset we have is a high-dimensional one, having 50K genes from 100 samples, with the issue of multicollinearity for fitting linear regression - the expression level of genes in the same pathway tends to be highly correlated. The property of LASSO with sparse parameters is naturally suitable to identify gene interactions of interest in this dataset. After biologically functional modules in the co-expression network was identified, the major changed expression patterns were further selected by LASSO regression to establish a linear relationship between gene expression profiles and physiological responses, such as sodium/potassium condenses, with salt stress. Five modules of intensively co-expressed genes, from 45 to 291 genes, were identified by our method with significant P-values, which indicate these modules are significantly associated with physiological responses to stress. Genes in these modules have functions related to ion transport, osmotic adjustment, and oxidative tolerance. For example, LOC_Os7g47350 and LOC_Os07g37320 are co-expressed gene in the same module 15. Both are ion transporter genes and have higher gene expression levels for rice with low sodium levels with salt stress.
Non-enzymatic roles of human RAD51 at stalled replication forks
Authors: Mason Jennifer M. , Chan Yuen-Ling , Weichselbaum Ralph W. , Bishop Douglas K.
Published: June 2018

The central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not strand exchange activity, to reveal mechanistic aspects of RAD51’s roles in the response to replication stress. We find that cells lacking RAD51 strand exchange activity protect replication forks from MRE11-dependent degradation, as expected from previous studies. Unexpectedly we find that RAD51’s strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2. Such conversion was shown previously to require replication fork reversal, supporting a model in which fork reversal depends on a non-enzymatic function of RAD51. We also show RAD51 promotes replication restart by both strand exchange-dependent and strand exchange-independent mechanisms.
A comparison of asymmetric before-after control impact (aBACI) and staircase experimental designs for testing the effectiveness of stream restoration
Authors: Loughin Tom M. , Bennett Stephen N. , Bouwes Nicolaas W.
Published: June 2018

Before-after-control-impact (BACI) experimental designs are commonly used in large-scale experiments to test for environmental impacts. However, high natural variability of environmental conditions and populations, and low replication in both treatment and control areas in time and space hampers detection of responses. We compare the power of two asymmetric BACI (aBACI) designs to two staircase designs for detecting changes in juvenile steelhead (Oncorhynchus mykiss) abundance associated with a watershed-scale stream restoration experiment. We performed a simulation study to estimate the effect of a 25% increase in steelhead abundance using spatial and temporal estimates of variance from an ongoing study, and determined the power of each design. Experimental designs were then applied to three streams and each stream was composed of three 4 km long sections. We compared the power of a single treatment section in one stream (BACI-1), three simultaneous treatments of all sections in one stream (BACI-3), three sequential treatments in one stream (STAIRCASE-1), and three sequential treatments in one section in each stream (STAIRCASE-3). All designs had ≥ 94% power to detect a 25% increase in abundance assuming average variance. Under worst-case variance (i.e., upper 95% confidence limits of historical variance estimates), the STAIRCASE-3 design outperformed the BACI-1, BACI-3, and STAIRCASE-1 designs (i.e., 77%, 41%, 8%, and 33% power respectively). All the designs estimated the effect of the simulated 25% abundance increase, but the length of the confidence interval was much shorter for the STAIRCASE-3 design compared to the other designs, which had confidence intervals 58-596% longer. The STAIRCASE-3 design continued to have high power (88%) to detect a 10% change in abundance, but the power of the other designs was much lower (range 34-56%). Our study demonstrates that staircase designs can have significant advantages over BACI designs and therefore should be more widely used for testing environmental impacts.
DNMT1 in Six2 progenitor cells is essential for transposable element silencing and kidney development
Authors: Li Szu-Yuan , Park Jihwan , Chung Kiwung , Shrestha Rojesh , Palmer Matthew B , Susztak Katalin
Published: June 2018

Cytosine methylation (5mC) plays a key role in maintaining progenitor cell self-renewal and differentiation. Here, we analyzed the role of 5mC in kidney development by genome-wide methylation, expression profiling, and by systematic genetic targeting of DNA methyltransferases (Dnmt) and Ten-eleven translocation methylcytosine hydroxylases (Tet).

In mice, nephrons differentiate from Six2+ progenitor cells, therefore we created animals with genetic deletion of Dnmt1, 3a, 3b, Tet1, and Tet2 in the Six2+ population (Six2Cre/Dnmt1flox/flox, Six2Cre/Dnmt3aflox/flox, Six2Cre/Dnmt3bflox/flox, Six2Cre/Tet2flox/flox and Tet1-/-). Animals with conditional deletion of Dnmt3a, 3b, Tet1 and Tet2 showed no significant structural or functional renal abnormalities. On the other hand, Six2Cre/Dnmt1flox/flox mice died within 24hrs of birth. Dnmt1 knock-out animals had small kidneys and significantly reduced nephron number. Genome-wide methylation analysis indicated marked loss of methylation mostly on transposable elements. RNA sequencing detected endogenous retroviral (ERV) gene transcripts and early embryonic genes. Increase in levels of interferon (and RIG-I signaling) and apoptosis (Trp53) in response to ERV activity likely contributed to the phenotype development. Once epithelial differentiation was established, loss of Dnmt1, 3a, 3b, Tet1 or Tet2 in glomerular epithelial cells did not lead to functional or structural differences at baseline or following toxic glomerular injury.

Genome-wide cytosine methylation and gene expression profiling showed that Dnmt1-mediated DNA methylation is essential for kidney development by preventing regression of progenitor cells into a primitive undifferentiated state and demethylation of transposable elements.

Significance

Cytosine methylation of regulatory regions (promoters and enhancers) has been proposed to play a key role in establishing gene expression and thereby cellular phenotype. DNMT1 is the key enzyme responsible for maintaining methylation patterns during DNA replication. While the role of Dnmt1 has been described in multiple organs, here we identified a novel, critically important mechanism how Dnmt1 controls tissue progenitors. The greatest methylation difference in Dnmt1 knock-out mice was observed on transposable elements (TE), which resulted in increase of endogenous retroviruses and cell death. We believe that release of TE was a critically overlooked component of phenotype development in previous studies that our comprehensive genome wide methylation analysis allowed us to identify.

Competing interests

The Susztak lab receives research support from Biogen, Boehringer Ingelheim, Celgene, GSK, Merck, Regeneron and ONO Pharma for work not related to this manuscript.
SummaryAUC: a tool for evaluating the performance of polygenic risk prediction models in validation datasets with only summary level statistics
Authors: Song Lei , Liu Aiyi ,   Molecular Genetics of Schizophrenia Consortium, Shi Jianxin
Published: June 2018

Motivation

Polygenic risk score (PRS) methods based on genome-wide association studies (GWAS) have a potential for predicting the risk of developing complex diseases and are expected to become more accurate with larger training data sets and innovative statistical methods. The area under the ROC curve (AUC) is often used to evaluate the performance of PRSs, which requires individual genotypic and phenotypic data in an independent GWAS validation dataset. We are motivated to develop methods for approximating AUC of PRSs based on the summary level data of the validation dataset, which will greatly facilitate the development of PRS models for complex diseases.

Results

We develop statistical methods and an R package SummaryAUC for approximating the AUC and its variance of a PRS when only the summary level data of the validation dataset are available. SummaryAUC can be applied to PRSs with SNPs either genotyped or imputed in the validation dataset. We examined the performance of SummaryAUC using a large-scale GWAS of schizophrenia. SummaryAUC provides accurate approximations to AUCs and their variances. The bias of AUC is typically less than 0.5% in most analyses. SummaryAUC cannot be applied to PRSs that use all SNPs in the genome because it is computationally prohibitive.

Availability

https://github.com/lsncibb/SummaryAUC

Contact

Jianxin.Shi@nih.gov
Third International Workshop on Improving Data Quality in XAFS Spectroscopy, Q2XAFS2017
Authors: Diaz-Moreno Sofia , Strange Richard W.
Published: June 2018

This issue of the Journal of Synchrotron Radiation is a special issue including papers from the Q2XAFS2017 workshop. Here, a brief introduction is given.
Marico – competing with an innovative business model
Authors: Mitra Sumit , V.K. Ranjith
Published: June 2018

Subject area

Strategic Management.

Study level/applicability

MBA, Executive MBA.

Case overview

This case deals with Harsh Mariwalla’s struggle to develop an innovative company from scratch. The journey of innovation is not an easy one. Marico was forced to compete with multinationals in many markets where it operated. Constant pressure from rivals has made the company develop a new innovative business model, which is expected to generate profitability and sustainable competitive advantage.

Expected learning outcomes

Students will be able to appreciate the business models, understand the competitive moves by rivals, understand strategy formulation and implementation, understand product innovation and competitive advantage and understand the ability to tackle competition with innovation.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 11: Strategy.
Toxic leadership in defense and federal workplaces: sabotaging the mission and innovation
Authors: Williams Kenneth R.
Published: June 2018

Purpose

Military officers and government officials have a duty to serve selflessly, without personal bias or favoritism, demonstrating effectiveness and the efficient use of resources for the safety, security and thriving of the people. However, some abuse subordinates for personal or professional gain. The purpose of this paper is to discuss toxic leadership, its cost, effects and impact and provides recommendations for prevention and intervention.

Design/methodology/approach

Based on survey research of a convenience sample of military and federal government students at the National Defense University, the paper does not allow for generalizability, but presents patterns and trends in descriptive statistics.

Findings

The sample of 186 reported an average of 2.9 toxic leaders in an average of 18.3 years of service. Student observations of the most toxic leader they served identified high prevalence of all toxic behaviors with the most prevalent being a lack of self-awareness, a negative interpersonal style, suspicion of others, passive hostility, defensiveness, refusal to allow dissent and shaming and blaming. The frequency and degree of impact on targets, witnesses, and teams of toxic leadership were significant, especially in avoidance, worry, and decreased contribution, motivation and productivity.

Practical implications

These results indicate that toxic leadership degrades military performance and readiness and government efficiency. Organizations can effectively address toxic leadership through purposeful, cultural reinforcement and leader development, increasing efficiency and reducing waste.

Originality/value

Although civilian and public research exists, this is the first and only such research in the military and federal government and lays a foundation for further study of these organizations.
The British Olympic football team
Authors: Hills Stephen , Heere Bob , Walker Matt
Published: June 2018

Purpose

The decision by the British Olympic Association to enter a soccer team into the Olympic Games of 2012, having not participated in the Olympic soccer competition since 1960, provided an opportunity to study representation as a predictor of fan identification. The paper aims to discuss this issue.

Design/methodology/approach

Using a quasi-experimental research design, the authors empirically validated the value of representation by comparing the identity levels of homogeneous samples of English and Scottish respondents toward the Great Britain Olympic National Football, participating in the Olympic Games of 2012.

Findings

Only partial support for four sets of hypotheses was found. In general, there seemed to be low levels of identity of each of the samples with the football team, because neither English nor Scottish respondents perceived the team to be representative of them. Nevertheless, the results support the general notion that representation is a valuable predictor of consumer identification.

Originality/value

Representation has been proposed as a central component of a sport team’s ability to serve as a symbol to their community, which enables the team to benefit from existing fan identities and the community the team is associated with. Yet, an empirical assessment of this phenomenon is lacking.
A flexible calibration method connecting the joint space and the working space of industrial robots
Authors: Cai Ying , Yuan Peijiang , Chen Dongdong
Published: June 2018

Purpose

To improve the accuracy of the industrial robots’ absolute positioning, a Kriging calibration is proposed.

Design/methodology/approach

This method particularly designs a semivariogram for connecting the joint space and the working space. After that, Kriging equations are determined and solved to predict the position errors of targets. Subsequently, a simple and convenient error compensation, which can be implemented on the control command, is proposed.

Findings

The verification experiment of the position-error multiplicity and the Kriging calibration experiment are done in the KUKA R210 R2700 industrial robot. The position-error multiplicity experiment reveals that the position error of the industrial robot varies with the joint angle sets. Besides, the Kriging calibration experiment shows that the maximum of the spatial position errors is reduced from 1.2906 to 0.2484 mm, which reveals the validity of the Kriging calibration.

Originality/value

The special designed semivariation allows this method to be flexible and practical. It can be used in various fields where the angle solutions of industrial robots should be adapted according to the optimal demand and the environment, such as the optimal trajectory planning and the obstacle avoidance. Besides, this method can provide accuracy positioning results.
Principals’ preferences when hiring teachers: a conjoint experiment
Authors: Giersch Jason , Dong Christopher
Published: June 2018

Purpose

What do principals look for when hiring teachers? The purpose of this paper is to extend the knowledge concerning what aspects of teacher quality are in demand among the individuals who administer schools and make hiring decisions.

Design/methodology/approach

Rather than employing interviews or surveys, the authors utilized a conjoint instrument that assembled teacher characteristics into fictitious applicant profiles. Participating North Carolina public school principals (n = 467) then chose among the computer-generated options and regression analysis allowed the authors to identify preferences in the aggregate.

Findings

Principals in this study preferred applicants with classroom experience, but those with 15 years were no more preferred than those with 5. They also preferred applicants with more education, but an advanced degree was no more preferred than a bachelor’s from a highly selective institution. Preference for teachers who are committed to state standards varied with schools’ performance on state tests.

Originality/value

Conjoint analysis is a useful tool for measuring preferences but is underutilized in research on education administration. This paper contributes not only to the body of knowledge about school principal behavior but also to the field’s familiarity of research techniques.