bluuebunny/crossref_metadata_2025 huggingface dataset:
NORTH: a highly accurate and scalable Naive Bayes based ORTHologous gene clustering algorithm
Authors: Ibtehaz Nabil , Ahmed Shafayat , Saha Bishwajit , Rahman M. Sohel , Bayzid Md. Shamsuzzoha
Published: January 2019

Background

The principal objective of comparative genomics is inferring attributes of an unknown gene by comparing it with well-studied genes. In this regard, identifying orthologous genes plays a pivotal role as the orthologous genes remain less diverged in the course of evolution. However, identifying orthologous genes is often difficult, slow, and idiosyncratic, especially in the presence of multiplicity of domains in proteins, evolutionary dynamics (gene duplication, transfer, loss, introgression etc.), multiple paralogous genes, incomplete genome data, and for distantly related species where similarity is hard to recognize.

Motivation

Advances in identifying orthologs have mostly been constrained to developing databases of genes or methods which involve computationally expensive BLAST search or constructing phylogenetic trees to infer orthologous relationships. These methods do not generally scale well and cannot analyze large amount of data from diverse organisms with high accuracy. Moreover, most of these methods involve manual parameter tuning, and hence are neither fully automated nor free from human bias.

Results

We present NORTH, a novel, automated, highly accurate and scalable machine learning based orhtologous gene clustering method. We have utilized the biological basis and intuition of orthologous genes and made an effort to incorporate appropriate ideas from machine learning (ML) and natural language processing (NLP). We have discovered that the BLAST search based protocols deeply resemble a “text classification” problem. Thus, we employ the robustbag-of-words modelaccompanied by a Naive Bayes classifier to cluster the orthologous genes. We studied 1,255,877 genes in the largest 250 ortholog clusters from the KEGG database, across 3,880 organisms comprising the six major groups of life, namely, Archaea, Bacteria, Animals, Fungi, Plants and Protists. Despite having more than a million of genes on distantly related species with acute data imbalance, NORTH is able to cluster them with 98.48% Precision, 98.43% Recall and 98.44%F1score, showing that automatic orthologous gene clustering can be both highly accurate and scalable. NORTH is available as a web interface with a server side application, along with cross-platform native applications (available athttps://nibtehaz.github.io/NORTH/) – allowing queries based on individual genes.
Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity
Authors: Weber Lilian A. , Diaconescu Andreea O. , Mathys Christoph , Schmidt André , Kometer Michael , Vollenweider Franz , Stephan Klaas E.
Published: January 2019

The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive coding or, more generally, the “Bayesian brain” notion that the brain continuously updates a hierarchical model to infer the causes of its sensory inputs. Specifically, predictive coding views perceptual inference as an NMDAR-dependent process of minimizing hierarchical precision-weighted prediction errors (PEs). Disturbances of this putative process play a key role in hierarchical Bayesian theories of schizophrenia.

Here, we provide empirical evidence for this clinical theory, demonstrating the existence of multiple, hierarchically related PEs in a “roving MMN” paradigm. We applied a computational model, the Hierarchical Gaussian Filter (HGF), to single-trial EEG data from healthy volunteers that received the NMDAR antagonist S-ketamine in a placebo-controlled, double-blind, within-subject fashion. Using an unrestricted analysis of the entire time-sensor space, our computational trial-by-trial analysis indicated that low-level PEs (about stimulus transitions) are expressed early (102-207ms post-stimulus), while high-level PEs (about transition probability) are reflected by later components (152-199ms, 215-277ms) of single-trial responses. Furthermore, we find that ketamine significantly diminished the expression of high-level PE responses, implying that NMDAR antagonism disrupts inference on abstract statistical regularities.

Our findings are consistent with long-standing notions that NMDAR dysfunction may cause positive symptoms in schizophrenia by impairing hierarchical Bayesian inference about the world’s statistical structure. Beyond their relevance for schizophrenia, our results illustrate the potential of computational single-trial analyses for assessing potential disease mechanisms.
Genetic Identification of Cell Types Underlying Brain Complex Traits Yields Novel Insights Into the Etiology of Parkinson’s Disease
Authors: Bryois Julien , Skene Nathan G. , Hansen Thomas Folkmann , Kogelman Lisette J.A. , Watson Hunna J. ,   Eating Disorders Working Group of the Psychiatric Genomics Consortium,   International Headache Genetics Consortium,   The 23andMe Research Team, Brueggeman Leo , Breen Gerome , Bulik Cynthia M. , Arenas Ernest , Hjerling-Leffler Jens , Sullivan Patrick F.
Published: January 2019

Genome-wide association studies (GWAS) have discovered hundreds of loci associated with complex brain disorders, and provide the best current insights into the etiology of these idiopathic traits. However, it remains unclear in which cell types these variants may be active, which is essential for understanding disease etiology and for disease modelling. Here we integrate GWAS results with single-cell transcriptomic data from the entire nervous system to systematically identify cell types underlying psychiatric disorders, neurological conditions, and other brain complex traits. We show that psychiatric disorders are predominantly associated with excitatory neurons from the cortex/hippocampus, medium spiny neurons from the striatum, diverse sets of midbrain neurons, and inhibitory neurons from the cortex/hippocampus. Cognitive traits were generally associated with similar cell types but their associations were driven by different genes. Neurological disorders were associated with different cell types, consistent with other lines of evidence. Notably, we found that Parkinson’s disease is not only genetically associated with dopaminergic neurons but also with serotonergic neurons and cells from the oligodendrocyte lineage. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Altogether, our study provides a solid framework for understanding the cellular basis of complex brain disorders and reveals a new unexpected role of oligodendrocytes in Parkinson’s disease.
Characterization of Spontaneously Arising Chlorhexidine-Tolerant Variants inStreptococcus mutans
Authors: Kaspar Justin R. , Godwin Matthew J. , Velsko Irina M. , Richards Vincent P. , Burne Robert A.
Published: January 2019

Broad spectrum antimicrobials, both in dental products and within the clinic, have been used in the suppression of cariogenic bacteria such asStreptococcus mutansfor over 40 years. One such antimicrobial is chlorhexidine (CHX), and serves as a standard in dental research against which other antimicrobial therapies are compared against for their efficacy. However, very little is known about the mode of action for CHX against Streptococci and whether tolerance can be developed from repeated exposures. Here, we begin to answer such questions by passagingS. mutanswith increasing concentrations of CHX and isolating spontaneously-arising tolerant variants (CTVs) from separate lineages. We find that these CTVs display a higher minimal inhibitory concentration (MIC) against CHX than the wild-type strain and have altered virulence properties such as acid tolerance and biofilm formation. We record higher MICs for the variants against both daptomycin and bacitracin, but find increased sensitivity to triclosan and sodium fluoride. Measurements of antagonistic capabilities against other health-associated oral streptococci show decreased bacteriocin production compared to wild-type and increased sensitivity to hydrogen peroxide. Finally whole genome sequencing of the CTVs show common single nucleotide polymorphisms (SNPs) within a diacylglycerol kinase homolog and a glycolipid synthesis enzyme, altering LTA accumulation and potentially lipid profile of the cell wall. Together, these findings confirm that streptococci may develop tolerance to antimicrobial agents such as CHX but in the case ofS. mutans,increased tolerance may come at a fitness cost for survival within oral biofilms that keeps variants suppressed within the population.
Mitohormetic effects of rotenone drastically depend on age
Authors: Baumgart Mario , Ugolini Martino , Groth Marco , Platzer Matthias , Cellerino Alessandro
Published: January 2019

Hormesis refers to a biphasic intensity-dependent response to stressors where low-intensity or short-duration exposure to potentially noxious stressors induces long-lasting adaptations that have positive physiological effects [1]. It was proposed that life-extending interventions, such as calorie restriction, retard aging via their hormetic action [2]. More recently, it was shown that a transient burst of reactive oxygen species is required to induce the effects of calorie restriction [3], physical exercise [4], inhibition of the insulin/IGF-I pathway [5] and metformin [6]. We have previously shown that partial inhibition of complex I of the respiratory chain by a low dose of the poison rotenone (ROT) administered in middle age increases the lifespan and reverts the transcriptomic signature of aging in a vertebrate species [7], an example of a hormetic effect. Here, we asked whether ROT treatment started at young age induces larger effects on life-span and transcriptome.
Cortical and subcortical neurons discriminate sounds in noise on the sole basis of acoustic amplitude modulations
Authors: Souffi S. , Lorenzi C. , Huetz C. , Edeline J-M
Published: January 2019

Humans and animals maintain accurate sound discrimination in the presence of loud sources of background noise. It is commonly assumed that this ability relies on the robustness of auditory cortex responses. However, no attempt has been made to characterize neural discrimination of sounds masked by noise at each stage of the auditory system and disentangle the sub-effects of noise, namely the distortion of temporal cues conveyed by modulations in instantaneous amplitude and frequency, and the introduction of randomness (stochastic fluctuations in amplitude). Here, we measured neural discrimination between communication sounds masked by steady noise in the cochlear nucleus, inferior colliculus, auditory thalamus, primary and secondary auditory cortex at several signal-to-noise ratios. Sound discrimination by neuronal populations markedly decreased in each auditory structure, but collicular and thalamic populations showed better performance than cortical populations at each signal-to-noise ratio. Comparison with neural responses to tone-vocoded sounds revealed that the reduction in neural discrimination caused by noise was mainly driven by the attenuation of slow amplitude modulation cues, with the exception of the cochlear nucleus that showed a dramatic drop in discrimination caused by the randomness of noise. These results shed new light on the specific contributions of subcortical structures to robust sound encoding, and demonstrate that neural discrimination in the presence of background noise is mainly determined by the distortion of the slow temporal cues conveyed by communication sounds.
Tempo of gene regulation in wild and cultivatedVitisspecies shows coordination between cold deacclimation and budbreak
Authors: Kovaleski Alisson P. , Londo Jason P.
Published: January 2019

Highlight

Faster deacclimation and budbreak phenology is related to a faster regulon rather than higher expression of specific genes. ABA is a master regulator of deacclimation.

Dormancy release, loss of cold hardiness and budbreak are critical aspects of the annual cycle of deciduous perennial plants. Molecular control of these processes is not fully understood, and genotypic variation may be important for climate adaptation. Single-node cuttings from wild (Vitis amurensis, V. riparia) and cultivatedVitisgenotypes (V. vinifera‘Cabernet Sauvignon’, ‘Riesling’) were collected from the field during winter and placed under forcing conditions. Cold hardiness was measured daily, and buds were collected for RNA-Seq until budbreak. Field-collected single-node cuttings of ‘Riesling’ were treated with abscisic acid (ABA), and cold hardiness and budbreak at 7 °C were tracked. WildVitisgenotypes had faster deacclimation and budbreak thanV. vinifera. Temperature-sensing related genes were quickly and synchronously differentially expressed in all genotypes. ABA synthesis was down-regulated in all genotypes, and exogenous ABA prevented deacclimation. Ethylene- and oxidative stress-related genes were transiently up-regulated. Growth-related genes were up-regulated and showed staggering similar to deacclimation and budbreak of the four genotypes. The gene expression cascade that occurs during deacclimation and budburst phenology of fast (wild) and slow (cultivated) grapevines appears coordinated and temporally conserved. This may extend to other temperate woody species and suggest constraints on identification of process-specific keystone genes.
A High-Throughput Screen of a Library of Therapeutics Identifies Substrates of P-glycoprotein
Authors: Lee Tobie D. , Lee Olivia W. , Brimacombe Kyle R. , Chen Lu , Guha Rajarshi , Lusvarghi Sabrina , Tebase Bethilehem G. , Klumpp-Thomas Carleen , Robey Robert W. , Ambudkar Suresh V. , Shen Min , Gottesman Michael M. , Hall Matthew D.
Published: January 2019

The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit brain penetration of many chemotherapy drugs. Although Food and Drug Administration guidelines require that potential interactions of investigational drugs with P-gp be explored, often this information does not enter into the literature. As such, we developed a high-throughput screen (HTS) to identify substrates of P-gp from a series of chemical libraries, testing a total of 10,804 compounds, most of which have known mechanisms of action. We used the CellTiter-Glo viability assay to test library compounds against parental KB-3-1 human cervical adenocarcinoma cells and the colchicine-selected sub-line KB-8-5-11 that over-expresses P-gp. KB-8-5-11 cells were also tested in the presence of a P-gp inhibitor (tariquidar) to assess reversability of transporter-mediated resistance. Of the tested compounds, a total of 90 P-gp substrates were identified including 55 newly identified P-gp substrates. Substrates were confirmed using an orthogonal killing assay against HEK-293 cells transfected with P-gp. We confirmed that AT7159 (cyclin-dependent kinase inhibitor); AT9283, (Janus kinase 2/3 inhibitor); ispinesib (kinesin spindle protein inhibitor); gedatolisib (PKI-587, phosphoinositide 3-kinase/mammalian target of rampamycin inhibitor); GSK-690693 (AKT inhibitor); and KW-2478 (heat shock protein 90 inhibitor) were substrates, and direct ATPase stimulation was assessed. ABCG2 was also found to confer high levels of resistance to AT9283, GSK-690693 and gedatolisib, while ispinesib, AT7519 and KW-2478 were weaker substrates. Combinations of P-gp substrates and inhibitors were assessed to demonstrate on-target synergistic cell killing. This data will be of use in determining understanding how chemotherapeutic agents will cross the blood-brain barrier.
Social hierarchy position in female mice is associated with plasma corticosterone levels and hypothalamic gene expression
Authors: Williamson Cait M. , Lee Won , Decasien Alexandra R. , Lanham Alesi , Romeo Russell D. , Curley James P.
Published: January 2019

Social hierarchies emerge when animals compete for access to resources such as food, mates or physical space. Wild and laboratory male mice have been shown to develop linear hierarchies, however, less is known regarding whether female mice have sufficient intrasexual competition to establish significant social dominance relationships. In this study, we examined whether groups of outbred CD-1 virgin female mice housed in a large vivaria formed social hierarchies. We show that females use fighting, chasing and mounting behaviors to rapidly establish highly directionally consistent social relationships. Notably, these female hierarchies are less linear, steep and despotic compared to male hierarchies. Female estrus state was not found to have a significant effect on aggressive behavior, though dominant females had elongated estrus cycles (due to increased time in estrus) compared to subordinate females. Plasma estradiol levels were equivalent between dominant and subordinate females. Subordinate females had significantly lower levels of basal corticosterone compared to dominant females. Analyses of gene expression in the ventromedial hypothalamus indicated that subordinate females have elevated ERα, ERβ and OTR mRNA compared to dominant females. This study provides a methodological framework for the study of the neuroendocrine basis of female social aggression and dominance in laboratory mice.
Leveraging functional annotation to identify genes associated with complex diseases
Authors: Liu Wei , Li Mo , Zhang Wenfeng , Zhou Geyu , Wu Xing , Wang Jiawei , Lu Qiongshi , Zhao Hongyu
Published: January 2019

To increase statistical power to identify genes associated with complex traits, a number of transcriptome-wide association study (TWAS) methods have been proposed using gene expression as a mediating trait linking genetic variations and diseases. These methods first predict expression levels based on inferred expression quantitative trait loci (eQTLs) and then identify expression-mediated genetic effects on diseases by associating phenotypes with predicted expression levels. The success of these methods critically depends on the identification of eQTLs, which may not be functional in the corresponding tissue, due to linkage disequilibrium (LD) and the correlation of gene expression between tissues. Here, we introduce a new method called T-GEN (Transcriptome-mediated identification of disease-associatedGens withEpigenetic aNnotation) to identify disease-associated genes leveraging epigenetic information. Through prioritizing SNPs with tissue-specific epigenetic annotation, T-GEN can better identify SNPs that are both statistically predictive and biologically functional. We found that a significantly higher percentage (an increase of 18.7% to 47.2%) of eQTLs identified by T-GEN are inferred to be functional by ChromHMM and more are deleterious based on their Combined Annotation Dependent Depletion (CADD) scores. Applying T-GEN to 207 complex traits, we were able to identify more trait-associated genes (ranging from 7.7 % to 102%) than those from existing methods. Among the identified genes associated with these traits, T-GEN can better identify genes with high (>0.99) pLI scores compared to other methods. When T-GEN was applied to late-onset Alzheimer’s disease, we identified 96 genes located at 15 loci, including two novel loci not implicated in previous GWAS. We further replicated 50 genes in an independent GWAS, including one of the two novel loci.

Author summary

TWAS-like methods have been widely applied to understand disease etiology using eQTL data and GWAS results. However, it is still challenging to discriminate the true disease-associated genes from those in strong LD with true genes, which is largely due to the misidentification of eQTLs. Here we introduce a novel statistical method named T-GEN to identify disease-associated genes considering epigenetic information. Compared to current TWAS methods, T-GEN can not only identify eQTLs with higher CADD scores and function potentials in gene-expression imputation models, but also identify more disease-associated genes across 207 traits and more genes with high (>0.99) pLI scores. Applying T-GEN in late-onset Alzheimer’s disease identified 96 genes at 15 loci with two novel loci. Among 96 identified genes, 50 genes were further replicated in an independent GWAS.
The complete mitochondrial genome of the Golden Birdwing butterflyTroides aeacus: insights into phylogeny and divergence times of the superfamily Papilionoidea
Authors: Dong Si-Yu , Jiang Guo-Fang , Liu Gang , Hong Fang , Hsu Yu-Feng
Published: January 2019

Background

The Lepidoptera is one of the largest insect orders. Previous studies on the evolution of Lepidoptera did not confidently place butterflies, and many relationships among superfamilies in the megadiverse clade Ditrysia remain largely uncertain. Here, we generated a molecular dataset with 78 species of lepidopterian insects, including a new complete mitochondrial genome (mitogenome) sequences of the Golden Birdwing Butterfly,Troides aeacus,which was listed in appendix II of CITES.

Methods

Based on the concatenated nucleotide sequences of 13 protein-coding genes, we constructed phylogenetic trees with Bayesian Inference (BI) and Maximum Likelihood (ML) methods, and calculated the divergence times of Lepidoptera.

Results

Monophyly of the Papilionoidea including skippers (Hesperiidae) is strongly supported by a high bootstrap value. Butterflies were placed sister to the remaining obtectomeran Lepidoptera, and the latter was grouped with high bootstrap supports. Additionally, Papilionidae probably diverged from the group (Hesperiidae + (Nymphalidae + Pieridae)) at 102.65 Mya, the Early Cretaceous.T. aeacusand the Golden kaiserihindTeinopalpus aureusdiverged in the Cretaceous of 85.32 Mya. The age of Papilionoidea indicates that the primary break up of Gondwana may have an effect on the current distributions of butterflies.
Resting state fMRI reveals differential effects of glucose administration on central appetite signalling in young and old adults
Authors: Peters Riccarda , White David J , Scholey Andrew
Published: January 2019

Background

Healthy aging has been associated with reduced appetite and energy intake, which can lead to loss of bodyweight and undernutrition and related health problems. The causes for the decline in caloric intake are multifactorial involving physiological and non-physiological processes.

Aims

Here we examined age-related, physiological changes in brain responses associated with macronutrient intake.

Methods

Using a randomized, double blind, balanced cross-over design, younger (n=16, aged 21-30) and older adults (n=16, aged 55-78) received a drink containing glucose and a taste-matched placebo after an overnight fast. Blood glucose and hunger were assessed at baseline and 20 minutes post-ingestion, after which participants underwent resting state functional magnetic resonance imaging (rsfMRI).

Results

Frequency dependent changes in slow-5 (0.01-0.027Hz) and slow-4 (0.027-0.073Hz) amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) of the blood oxygen level-dependent (BOLD) signal were contrasted between sessions and age groups. We observed a significant treatment x age-group interaction in slow-5 ALFF and fALFF in the left insula. Younger participants showed a decrease in BOLD amplitude, whereas older participants showed an increase. We further observed a treatment x age-group interaction in slow-4 ALFF in the occipital and lingual gyrus and precuneus with older participants showing an increase in magnitude of slow-4 ALFF and younger participants showing a decrease in the same measure.

Conclusion

These age-related, frequency-dependent changes in the magnitude of the BOLD signal in a key region related to energy homeostasis following feeding may contribute to behavioral changes in energy intake during senescence.
Social context and dominance status contribute to sleep patterns and quality in groups of freely-moving mice
Authors: Karamihalev Stoyo , Flachskamm Cornelia , Kimura Mayumi , Chen Alon
Published: January 2019

In many socially-living species, sleep patterns are subject to group influences, as individuals adjust to the presence, daily rhythms, and social pressures inherent to cohabitation. Disturbances in social functioning are comorbid with sleep problems in many prevalent psychiatric disorders, most notably, autism-spectrum, mood, and anxiety disorders (e.g., [1-3]). Our understanding of the common causality and the interplay between sleep impairment and psychiatric symptomatology could greatly benefit from experimental paradigms that allow simultaneous assessment of both domains of functioning. In laboratory mice, much is known about the sensitivity of sleep quality to a variety of experimental manipulations. Due to existing methodological restrictions, however, sleep studies are typically conducted in single-housed mice, thereby neglecting the influence of social dynamics and group-derived individual differences (however, see [4,5]). Here, we investigated sleep in a semi-naturalistic environment with freely-moving socially-housed groups of male mice using wireless electroencephalographic (EEG) monitoring devices and automated video tracking. In addition to multiple days of continuous behavioral data, we collected over fifty hours of EEG signal per mouse, recording simultaneously from all individuals in a group. We found evidence of in-group synchrony of sleep state patterns. Moreover, social status was a powerful predictor of sleep quality, such that sleep fragmentation, slow-wave sleep power, and rapid eye movement (REM) episode duration differed as a function of dominance status in the group. Finally, acute stress exposure had differential effects on REM sleep during recovery in dominant versus subordinate individuals. These findings highlight the importance of exploring sleep in a social context and are a step toward more informative research on the interplay between social functioning and sleep.
The impact of coregistration of gradient recalled echo images on quantitative susceptibility and R2* mapping at 7T
Authors: Choi Seongjin , Li Xu , Harrison Daniel M.
Published: January 2019

Introduction

While image coregistration is inevitable and quantitative parametric maps, such as R2* and QSM, are increasingly used in multi-parametric studies of the brain, there is a lack of investigations on the reliability of quantitative metrics after coregistration. The purposes of this study were 1) to evaluate the reliability of R2* and QSM at 7T and 2) to assess the statistical agreement in the quantitative metrics obtained by two different coregistration approaches.

Methods

We compared the reliability of R2* and quantitative susceptibility maps obtained from brains of eight healthy participants by two coregistration approaches: 1) transformation of pre-processed quantitative maps and 2) processing quantitative maps after transformation using pixel- and ROI-based analyses. Two-sample Kolmogorov-Smirnov, Mann-Whitney U, Paired T, Intraclass-correlation tests were performed appropriately.

Results

R2* remained invariant regardless of the cogeneration timing. However, magnetic susceptibility was significantly altered when processed in transformed space, whereas it remained invariant in all KS-tests and pixel values were only different in 2 out of 64 U-tests for direct QSM coregistration. Paired t-test revealed that ROI-based group-mean R2* was invariant to both approaches, while group-mean susceptibility was invariant to direct coregistration but differed in one structure processed in transformed space. For all pairs of measurements of R2*, ICCs were excellent. ICCs for magnetic susceptibility were excellent when processed in its native space while the ICCs were lower than 0.9 or poor when processed in transformed space. Further analysis revealed that the choice of interpolation approach affected the resultant QSM.

Conclusions

Our study shows that R2* could be safely processed in a transformed space, whereas QSM was less reliable when processed in the transformed space. Hence, caution is advised when using QSM in a multi-parametric study, and it is strongly recommended to process QSM in its native space prior to any coregistration or spatial transformation.
Cold Shock Fail to Restrain Pre-formedVibrio parahaemolyticusBiofilm
Authors: Yu Wenying , Han Qiao , Song Xueying , Fu Jiaojiao , Liu Haiquan , Guo Zhuoran , Malakar Pradeep K , Pan Yingjie , Zhao Yong
Published: January 2019

The source of persistent infections can be biofilms that occur naturally on food surfaces and medical biomaterials. Biofilm formation on these materials are likely to be affected by environmental temperature fluctuations and information on noticeable temperature shifts on the fate of pre-formed biofilm is sparse. Changes to pre-formedVibrio parahaemolyticusbiofilm under cold shock (4 °C and 10 °C) was explored in this study. We show thatV. parahaemolyticusbiofilm biomass increased significantly during this cold shock period and there was a gradual increase of polysaccharides and proteins content in the extracellular polymeric matrix (EPS). In addition, we demonstrate that the expression of flagella and virulence-related genes were differentially regulated. The architecture of the biofilm, quantified using mean thickness (MT), average diffusion distance (ADD), porosity (P), biofilm roughness (BR) and homogeneity (H) also changed during the cold shock and these parameters were correlated (P < 0.01). However, the correlation between biofilm architecture and biofilm-related genes expression was relatively weak (P < 0.05). Cold shock at 4 °C and 10 °C is not sufficient to reduceV. parahaemolyticusbiofilm formation and strategies to reduce risk of foodborne infections should take this information into account.
Epidemiology ofStaphylococcus aureusin Neonates on Admission to a Chinese Neonatal Intensive Care Unit
Authors: Geng Wenjing , Qi Yujie , Li Wenting , McConvillle Thomas H. , Hill-Ricciuti Alexandra , Grohs Emily , Saiman Lisa , Uhlemann Anne-Catrin
Published: January 2019

Purpose

Little is known about the molecular epidemiology ofStaphylococcus aureusin Chinese neonatal intensive care units (NICUs). We describe the molecular epidemiology ofS. aureusisolated from neonates on admission to Beijing Children’s Hospital.

Methods

From May 2015-March 2016, nasal swabs were obtained on admission from 536 neonates. Cultures were also obtained from body sites with suspected infections.S. aureusisolates were characterized by staphylococcal chromosomal cassette (SCCmec) type, staphylococcal protein A (spa) type, multilocus sequence type (MLST),sasXgene, antimicrobial susceptibility and cytotoxicity. Logistic regression assessed risk factors for colonization.

Results

Overall, 92 (18%) infants were colonized withS. aureusand 23 (4%) were diagnosed with culture-positiveS. aureusinfection. Of the colonized infants, 72% harbored MSSA, while 74% of infected infants were culture-positive for MRSA. Risk factors for colonization included female sex, age 7-28 days, birthweight and vaginal delivery. The most common MRSA and MSSA clones were community-associated ST59-SCCmecIVa-t437 (60%) and ST188-t189 (15%), respectively. ThesasXgene was not detected. Some MSSA isolates (16%) were penicillin-susceptible and some MRSA isolates (18%) were oxacillin-susceptible. MRSA and MSSA had similar cytotoxicity, but colonizing strains were less cytotoxic than strains associated with infections.

Conclusions

S. aureuscolonization was common in infants admitted to our NICU and two community-associated clones predominated. Several non-modifiable risk factors forS. aureuscolonization were identified. These results suggest that screening infants forS. aureusupon admission and targeting decolonization of high-risk infants and/or those colonized with high-risk clones could be useful to prevent transmission.
Oscillations, criticality and responsiveness in complex brain networks
Authors: Kim MinKyung , Lee UnCheol
Published: January 2019

Brain networks during unconscious states resulting from sleep, anesthesia, or traumatic injuries are associated with a limited capacity for complex responses to stimulation. Even during the conscious resting state, responsiveness to stimulus is highly dependent on spontaneous brain activities. Many empirical findings have been suggested that the brain responsiveness is determined mainly by the ongoing brain activity when a stimulus is given. However, there has been no systematic study exploring how such various brain activities with high or low synchronization, amplitude, and phase response to stimuli. In this model study, we simulated large-scale brain network dynamics in three brain states (below, near, and above the critical state) and investigated a relationship between ongoing oscillation properties and a stimulus decomposing the brain activity into fundamental oscillation properties (instantaneous global synchronization, amplitude, and phase). We identified specific stimulation conditions that produce varying levels of brain responsiveness. When a single pulsatile stimulus was applied to globally desynchronized low amplitude of oscillation, the network generated a large response. By contrast, when a stimulus was applied to specific phases of oscillation that were globally synchronized with high amplitude activity, the response was inhibited. This study proposes the oscillatory conditions to induce specific stimulation outcomes in the brain that can be systematically derived from networked oscillator properties, and reveals the presence of state-dependent temporal windows for optimal brain stimulation. The identified relationship will help advance understanding of the small/large responsiveness of the brain in different states of consciousness and suggest state-dependent methods to modulate responsiveness.

Author Summary

A responsiveness of the brain network to external stimulus is different across brain states such as wakefulness, sleep, anesthesia, and traumatic injuries. It has been shown that responsiveness of the brain during conscious state also varies due to the diverse transient states of the brain characterized by different global and local oscillation properties. In this computational model study using large-scale brain network, we hypothesized that the brain responsiveness is determined by the interactions of networked oscillators when a stimulus is applied to the brain. We examined relationships between responsiveness of the brain network, global synchronization levels, and instantaneous oscillation properties such as amplitude and phase in different brain states. We found specific stimulation conditions of the brain that produce large or small levels of responsiveness. The identified relationship suggests the existence of temporal windows that periodically inhibit sensory information processing during conscious state and develops state-dependent methods to modulate brain responsiveness considering dynamically changed functional brain network.
JACKS: joint analysis of CRISPR/Cas9 knockout screens
Authors: Allen Felicity , Behan Fiona , Khodak Anton , Iorio Francesco , Yusa Kosuke , Garnett Mathew , Parts Leopold
Published: January 2019

Genome-wide CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. However, their range of applications remains limited by signal variability from different guide RNAs that target the same gene, which confounds gene effect estimation and dictates large experiment sizes. To address this problem, we report JACKS, a Bayesian method that jointly analyzes screens performed with the same guide RNA library. Modeling the variable guide efficacies greatly improves hit identification over processing a single screen at a time and outperforms existing methods. This more efficient analysis gives additional hits and allows designing libraries with a 2.5-fold reduction in required cell numbers without sacrificing performance compared to current analysis standards.
Design of the variable frequency oscillator in DC-DC converter
Authors: Lei Tian , Gong Nan , Wang Li , Li Qin Qin , Wang Heng Wei
Published: January 2019

Purpose

Because of the logic delay in the converter, the minimum turn on time of the switch is influenced by the constant time. When the inductor current gets to the threshold of the chip, the control signal will delay for a period. This makes the inductor current rising with the increasing of the clock and leads to the load current out of control. Thus, this paper aims to design an oscillator with a variable frequency protection function.

Design/methodology/approach

This paper presents an oscillator with the reducing frequency applied in the DC-DC converter. When the converter works normally, the operating frequency of the oscillator is 1.5 MHz. So the inductor current has enough time to decay and prevent the power transistor damaging. After the abnormal condition, the converter returns to the normal operating mode automatically.

Findings

Based on 0.5 µm CMOS process, simulated by the HSPICE, the simulation results shows that the frequency of the oscillator linearly decreases from 1.5 MHz to 380 KHz when the feedback voltage less than 0.2 V. The maximum deviation of the oscillator frequency is only 6 per cent from −50°C to 125°C within the power supply voltage of 2.7-5.5 V.

Originality/value

When the light load occurs at the output stage, the oscillator frequency will decrease as the load voltage drops. The test results shows that when the circuit works in the normal condition, the oscillator frequency is 1.5 MHz. When the load decreased, the operating frequency is dropped dramatically.
Applying the HUL approach to walled towns of Mediterranean seaport cities
Authors: Colavitti Anna Maria , Usai Alessia
Published: January 2019

Purpose

In last year, the innovations in shipbuilding and logistics have opened the walled towns of Mediterranean port cities to cruise tourism and other culture-led regeneration strategies. Thus, walled towns in Mediterranean port cities have a particular development potential which questions about the opportunities and risks connected to any comprehensive regeneration strategy with a cultural and tourist purpose, especially for fortified systems whose continuity has been undermined. The paper aims to provide some guidelines for policy-makers and planners in port cities which have decided or are deciding to develop a comprehensive strategy and a knowledge framework for the walled town similar to those already adopted for fortified sites in the World Heritage List.

Design/methodology/approach

The paper investigates on the opportunities and risks connected to any comprehensive regeneration strategy with a cultural and tourist purpose for the walled towns through a comparative analysis of four Mediterranean seaport cities, selected as case studies. Cities which have developed an integrated strategy to inscribe their walled towns to the UNESCO’s World Heritage List.

Findings

On the base of the case studies’ analysis, the paper proposes a critical reflection upon the management strategies for the UNESCO’s walled towns and supports a better understating of context factors as a way to strengthen the HUL approach when applied to Mediterranean seaport cities.

Originality/value

The paper sheds light on the application of the historic urban landscape approach to the walled towns of Mediterranean seaport cities. The paper is original because it provides: guidelines for policy-makers and planners in walled towns of Mediterranean seaport cities which have decided or are deciding to develop a comprehensive regeneration strategy for the city centre in line with those adopted in UNESCO’s fortified sites; a critical reflection upon the context factors which can strengthen the HUL approach when applied to Mediterranean seaport cities; criteria to update the HUL approach by UNESCO in analysing the conservation state, the managerial aspects, the participation and social aspects of walled towns.
Content validity of the WorkHab functional capacity evaluation
Authors: James Carole , MacKenzie Lynette , Capra Mike
Published: January 2019

Introduction

Validity is a dynamic process and as part of a continual process of evaluation of tools, this study aimed to evaluate content validity of the WorkHab functional capacity evaluation, a tool used in occupational rehabilitation.

Methods

A cross sectional survey of health professionals who conduct FCEs investigated their ratings of item relevance and item difficulty across different categories of work and injuries. The survey also explored the relationship of the WorkHab FCE items with the physical demand items of the Dictionary of Occupational Titles (DOT).

Results

The majority of items of the WorkHab FCE were rated as relevant for manual work and vocational retraining with over 90% agreement between the 106 respondents. Therapists identified the WorkHab items of climbing, crawling and balance as less relevant for sedentary work. Lifting items were perceived as the most difficult for those with a lower back injury, or an upper limb injury. Sixteen of the 18 WorkHab FCE items had 100% agreement with the equivalent items on the DOT. The WorkHab FCE items that had poor agreement with the DOT were mainly sensory items such as see, feel, talk and hear.

Conclusions

The findings of this study support the content validity for the WorkHab FCE specifically in relation to manual work and for vocational retraining purposes.
A realist evaluation of peer mentoring support for university students with autism
Authors: Thompson Craig , Falkmer Torbjörn , Evans Kiah , Bölte Sven , Girdler Sonya
Published: January 2019

Education is effective in improving outcomes in autism spectrum disorder (ASD). While peer mentoring has demonstrated preliminary promise in supporting university students with ASD, the effective mechanisms remain unclear. The aims of this study were to explore the required contexts, mechanisms and outcomes of peer mentoring for university students with ASD. Semi‐structured interviews based on a Realist Evaluation framework were conducted with 23 peer mentors and 24 university students with ASD. Thematic analysis identified three context themes: ‘environmental conditions’, ‘university course demands’ and ‘aspects of ASD’; four mechanism themes: ‘mentor’, ‘communication and social interaction’, ‘problem solving’ and ‘training and supervision’; and five outcome themes: ‘identifying personal strengths’, ‘increased autonomy’, ‘achieving goals’, ‘relationships’ and ‘positive mentor outcomes’. Standard peer mentoring approaches can be enhanced to meet the needs of students with ASD by including training for mentors on ASD, and approaches that support mentees’ social interaction and communication needs.
Cheating or legitimate support? Student‐Teachers’ attitudes toward digital tools in school
Authors: Karlsudd Peter
Published: January 2019

Sweden has easy access to digital technology, and the majority of the country’s teachers have good digital skills. Despite this, in comparison with teachers in other European countries, there are few teachers who integrate digital tools on a daily basis into their teaching. It is not uncommon for computers and word‐processing programmes in the realm of schooling to be regarded as compensatory aids for pupils who need special support. For written examinations, usually the only implements permitted are pencil and paper, and at most schools to use the computer requires special certification. The present study has investigated future teachers’ attitudes toward digital tools and their willingness to allow pupils to use these to help them read and produce texts. How do student‐teachers regard digital artifacts? Do they see these as compensatory aids or daily, legitimate tools? Are there any significant differences in their views depending on the type of teacher education programme or how far the student has advanced in his or her education? To investigate these questions, an online survey was conducted in which 247 students from five different teacher education programmes participated. The results show that future teachers’ acceptance of digital tools is varied. Roughly, one can divide the respondents into three groups, where the first group, making up more than a third, has clearly a positive attitude toward the use of digital tools in instruction. The second group, which makes up a smaller proportion, has an ambivalent stance towards the use of digital tools and expresses uncertainty in questions regarding their use in instruction and during examinations. The third group is much more reserved about ICT‐use in school and in several cases openly negative. Based on these results, it is critical to discuss how the different types of teachers can ensure equivalence in the school mission. If teacher education wants to work towards encouraging and legitimizing the use of digital resources, there must be a clear effort made in their education and application. That knowledge and skills open up for change is one of the most important results shown in this study.
Guiding Teachers of Students with Visual Impairments to Make Assistive Technology Decisions: Preliminary Experience Using the Wisconsin Assistive Technology Initiative
Authors: Wong Meng Ee
Published: January 2019

Despite the availability of assistive technology frameworks as a tool to aid in the process of decision making, teachers of students with visual impairments in Singapore have had little awareness of or experience in using such frameworks to guide them when making choices about assistive technology. Much of the selection had previously been made mainly on observations, intuitions and general recommendations, rendering the decision‐making task subjective and overwhelming. This article presents the trial experience of three teachers with the Wisconsin Assistive Technology Initiative (WATI). Participants compared and contrasted their experience with and without WATI in their work with students, reflecting on its application to their work. While the systematic approach towards considering assistive technology emerged as a strong reason for the framework, administrative demands including time and knowledge in assistive technology were some reported challenges. This article reports on the teachers’ initial impressions and puts forward some recommendations for adopting WATI.
Invisible Evidence: Our Disconnection with Broadband Connectivity
Authors: FAULKNER SUSAN
Published: January 2019

When our broadband connectivity at home stops working, it's a crisis. When it does work it is magic, an invisible miracle most of us don't understand. Our evidence for whether it is working great or barely working at all, is scant, murky and elusive. The telecommunications industry language used to measure and characterize connectivity is obtuse. Data transfer rates, data storage rates, and wireless frequency rates, all sound similar and make no sense to most people. So, what's wrong with that? Who cares how many megabits per second download speed I'm getting? As long as I can stream The Crown, what difference does it make? That's what I thought when I began doing research about people's relationships with connectivity, and then I met people who changed my point of view. Connectivity is fundamental to how we experience the world and to our sense of well‐being. We need ways to connect with our connectivity.
Working with Intuition
Authors: NANGIA ANISH
Published: January 2019

Evidence, today, can have very narrow definitions. For digital products, this type of evidence usually includes clicks and engagement metrics. I believe that in our effort to only listen to numbers and data, we have created a culture that looks down on intuition as something messy and to be rejected. As a result, we train ourselves to cast our intuition aside. When we do listen, we dare not speak up about it.

Intuition is a part of what makes us human. It is often the primary way we make sense of our work (and the world around us). Yet, we continue to focus only on rationality and logic. Ultimtately, the goal of this piece is to present intuition from a different lens – to understand it, learn to listen to it and create spaces where we talk about it.