bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population
Authors: Hill Sarah C. , Hansen Rowena , Watson Samantha , Coward Vivien , Russell Christine , Cooper Jayne , Essen Steve , Everest Holly , Parag Kris V. , Fiddaman Steven , Reid Scott , Lewis Nicola , Brookes Sharon M. , Smith Adrian L. , Sheldon Ben , Perrins Christopher M. , Brown Ian H. , Pybus Oliver G.
Published: May 2019

Understanding the epidemiological dynamics of highly pathogenic avian influenza virus (HPAIV) in wild birds is crucial for guiding effective surveillance and control measures. The spread of H5 HPAIV has been well characterized over large geographical and temporal scales. However, information about the detailed dynamics and demographics of individual outbreaks in wild birds is rare and important epidemiological parameters remain unknown. We present data from a wild population of long-lived birds (mute swans;
Cygnus olor
) that has experienced three outbreaks of related H5 HPAIVs in the past decade, specifically, H5N1 (2007), H5N8 (2016) and H5N6 (2017). Detailed demographic data were available and intense sampling was conducted before and after the outbreaks; hence the population is unusually suitable for exploring the natural epidemiology, evolution and ecology of HPAIV in wild birds. We show that key epidemiological features remain remarkably consistent across multiple outbreaks, including the timing of virus incursion and outbreak duration, and the presence of a strong age-structure in morbidity that likely arises from an equivalent age-structure in immunological responses. The predictability of these features across a series of outbreaks in a complex natural population is striking and contributes to our understanding of HPAIV in wild birds.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
Virus epidemics, plant-controlled population bottlenecks and the durability of plant resistance
Authors: Rousseau Elsa , Bonneault Mélanie , Fabre Frédéric , Moury Benoît , Mailleret Ludovic , Grognard Frédéric
Published: May 2019

Plant qualitative resistances to viruses are natural exhaustible resources that can be impaired by the emergence of resistance-breaking (RB) virus variants. Mathematical modelling can help determine optimal strategies for resistance durability by a rational deployment of resistance in agroecosystems. Here, we propose an innovative approach, built up from our previous empirical studies, based on plant cultivars combining qualitative resistance with quantitative resistance narrowing population bottlenecks exerted on viruses during host-to-host transmission and/or within-host infection. Narrow bottlenecks are expected to slow down virus adaptation to plant qualitative resistance. To study the effect of bottleneck size on yield, we developed a stochastic epidemic model with mixtures of susceptible and resistant plants, relying on continuous-time Markov chain processes. Overall, narrow bottlenecks are beneficial when the fitness cost of RB virus variants in susceptible plants is intermediate. In such cases, they could provide up to 95 additional percentage points of yield compared with deploying a qualitative resistance alone. As we have shown in previous works that virus population bottlenecks are at least partly heritable plant traits, our results suggest that breeding and deploying plant varieties exposing virus populations to narrowed bottlenecks will increase yield and delay the emergence of RB variants.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
Quantifying the consequences of measles-induced immune modulation for whooping cough epidemiology
Authors: Noori Navideh , Rohani Pejman
Published: May 2019

Measles, an acute viral disease, continues to be an important cause of childhood mortality worldwide. Infection with the measles virus is thought to be associated with a transient but profound period of immune suppression. Recently, it has been claimed that measles-induced immune manipulation lasts for about 30 months and results in increased susceptibility to other co-circulating infectious diseases and more severe disease outcomes upon infection. We tested this hypothesis using model-based inference applied to parallel historical records of measles and whooping cough mortality and morbidity. Specifically, we used maximum likelihood to fit a mechanistic transmission model to incidence data from three different eras, spanning mortality records from 1904 to 1912 and 1922 to 1932 and morbidity records from 1946 to 1956. Our aim was to quantify the timing, severity and pathogenesis impacts of measles-induced immune modulation and their consequences for whooping cough epidemiology across a temporal gradient of measles transmission. We identified an increase in susceptibility to whooping cough following recent measles infection by approximately 85-, 10- and 36-fold for the three eras, respectively, although the duration of this effect was variable. Overall, while the immune impacts of measles may be strong and clearly evident at the individual level, their epidemiological signature in these data appears both modest and inconsistent.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
Detection, forecasting and control of infectious disease epidemics: modelling outbreaks in humans, animals and plants
Authors: Thompson Robin N. , Brooks-Pollock Ellen
Published: May 2019

The 1918 influenza pandemic is one of the most devastating infectious disease epidemics on record, having caused approximately 50 million deaths worldwide. Control measures, including prohibiting non-essential gatherings as well as closing cinemas and music halls, were applied with varying success and limited knowledge of transmission dynamics. One hundred years later, following developments in the field of mathematical epidemiology, models are increasingly used to guide decision-making and devise appropriate interventions that mitigate the impacts of epidemics. Epidemiological models have been used as decision-making tools during outbreaks in human, animal and plant populations. However, as the subject has developed, human, animal and plant disease modelling have diverged. Approaches have been developed independently for pathogens of each host type, often despite similarities between the models used in these complementary fields. With the increased importance of a One Health approach that unifies human, animal and plant health, we argue that more inter-disciplinary collaboration would enhance each of the related disciplines. This pair of theme issues presents research articles written by human, animal and plant disease modellers. In this introductory article, we compare the questions pertinent to, and approaches used by, epidemiological modellers of human, animal and plant pathogens, and summarize the articles in these theme issues. We encourage future collaboration that transcends disciplinary boundaries and links the closely related areas of human, animal and plant disease epidemic modelling.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
TractEM: Fast Protocols for Whole Brain Deterministic Tractography-Based White Matter Atlas
Authors: Bayrak Roza G. , Wang Xuan , Schilling Kurt G. , Greer Jasmine M. , Hansen Colin B. , Blaber Justin A. , Williams Owen , Beason-Held Lori L. , Resnick Susan M. , Rogers Baxter P. , Landman Bennett A.
Published: May 2019

Reproducible identification of white matter tracts across subjects is essential for the study of structural connectivity of the human brain. The key challenges are anatomical differences between subjects and human rater subjectivity in labeling. Labeling white matter regions of interest presents many challenges due to the need to integrate both local and global information. Clearly communicating the human/manual processes to capture this information is cumbersome, yet essential to lay a solid foundation for comprehensive atlases. The state-of-the-art for white matter atlas is the single population-averaged Johns Hopkins Eve atlas. A critical bottleneck with the Eve atlas framework is that manual labeling time is extensive and peripheral white matter regions are conservatively labeled. In this work, we developed protocols that will facilitate manual virtual dissection of white matter pathways, with the goals to be anatomically accurate, intuitive, reproducible, and act as an initial stage to build an amenable knowledge base of neuroanatomical regions. We analyzed reproducibility of the fiber bundles and variability of human raters using DICE correlation coefficient, intraclass correlation coefficient, and root mean squared error. The protocols at their initial stage have shown promising results on both typical 3T research acquisition Baltimore Longitudinal Study of Aging and high-acquisition quality Human Connectome Project datasets. The TractEM manual labeling protocols allow for reconstruction of reproducible subject-specific fiber bundles across the brain. The protocols and sample results have been made available in open source to improve generalizability and reliability in collaboration.
Estimating Rates of Progression and Predicting Future Visual Fields in Glaucoma Using a Deep Variational Autoencoder
Authors: Berchuck Samuel I. , Mukherjee Sayan , Medeiros Felipe A.
Published: May 2019

Purpose

To develop a novel deep learning algorithm to improve estimation of rates of progression and prediction of future patterns of visual field loss in glaucoma.

Design

Prospective observational cohort.

Methods

A variational auto-encoder (VAE) was trained to learn a low-dimensional feature representation of standard automated perimetry (SAP) visual fields using 29,161 fields from 3,832 patients. The VAE was trained on a 90% sample of the data, with randomization at the patient level. Using the remaining 10%, rates of progression and predictions were generated, with comparisons to SAP mean deviation (MD) rates and point-wise (PW) regression predictions, respectively. From the VAE, rates were calculated using the average of slopes across latent features from ordinary least squares (OLS) regression and trajectories of the features were used to generate predictions.

Results

The longitudinal rate of change through the VAE latent space (e.g., with eight dimensions) detected a significantly higher proportion of progression than MD at two (19% vs. 6%) and four (40% vs 14%) years from baseline. Early on, VAE improved prediction over PW, with significantly smaller mean absolute error in predicting the 4th, 6th and 8th visits from the first three (e.g., visit eight: VAE8: 4.06 dB vs. PW: 6.06 dB; P<0.001).

Conclusion

A deep VAE can be used for assessing both rates and trajectories of progression in glaucoma, with the additional benefit of being a generative technique capable of predicting future patterns of visual field damage in the disease.
Effects of Serotonin and Dopamine Depletion on Neural Prediction Computations during Social Learning
Authors: Frey Anna-Lena , McCabe Ciara
Published: May 2019

We recently found that individuals with high depression scores demonstrate impaired learning from social outcomes. Given that depression has been linked to altered serotonin (5-HT) and dopamine (DA) functioning, the current study aimed to elucidate the role of these neurotransmitters in social learning with the use of dietary precursor depletion. In a double-blind design, 70 healthy volunteers were randomly allocated to the 5-HT depletion (N=24), DA depletion (N = 24), or placebo (N = 22) group. Participants performed a social learning task during fMRI scanning, as part of which they learned associations between name cues and rewarding (happy faces) or aversive (fearful faces) social outcomes. Behaviourally, 5-HT depleted subjects demonstrated impaired social reward learning compared to placebo controls, with a marginal effect in the same direction in the DA depletion group. On the neural level, computational modelling-based fMRI analyses revealed that 5-HT depletion altered social reward prediction signals in the insula, temporal lobe, and prefrontal cortex. DA depletion affected social reward prediction encoding only in the prefrontal cortex. These results indicate that 5-HT depletion impairs learning from social rewards, on both the behavioural and the neural level, while DA depletion has a less extensive effect. Interestingly, the behavioural and neural responses observed after 5-HT depletion in the current study closely resemble our previous findings in individuals with high depression scores. It may thus be the case that decreased 5-HT levels contribute to social learning deficits in depression.
The categorical neural organization of speech aids its perception in noise
Authors: Bidelman Gavin M. , Bush Lauren C. , Boudreaux Alex M.
Published: May 2019

We investigated whether the categorical perception (CP) of speech might also provide a mechanism that aids its perception in noise. We varied signal-to-noise ratio (SNR) [clear, 0 dB, -5 dB] while listeners classified an acoustic-phonetic continuum (/u/ to /a/). Noise-related changes in behavioral categorization were only observed at the lowest SNR. Event-related brain potentials (ERPs) differentiated phonetic vs. non-phonetic (category ambiguous) speech by the P2 wave (∼180-320 ms). Paralleling behavior, neural responses to speech with clear phonetic status (i.e., continuum endpoints) were largely invariant to noise, whereas responses to ambiguous tokens declined with decreasing SNR. Results demonstrate that phonetic speech representations are more resistant to degradation than corresponding acoustic representations. Findings suggest the mere process of binning speech sounds into categories provides a robust mechanism to aid perception at the “cocktail party” by fortifying abstract categories from the acoustic signal and making the speech code more resistant to external interferences.
Antioxidants maintain Butyrate production by Human GutClostridiain the presence of Oxygen
Authors: Million Matthieu , Armstrong Nicholas , Khelaifia Saber , Guilhot Elodie , Richez Magali , Lagier Jean-Christophe , Dubourg Gregory , Chabriere Eric , Raoult Didier
Published: May 2019

Background

Oxygen diffused from the human gut mucosa and shape the microbiota with a radial gradient of microbes according to their oxygen tolerance, while microbial and chemical oxygen consumption maintains the lumen in a deeply anaerobic state. Uncontrolled oxidative stress and hyperoxygenation have been reported as a pathogenic mechanism inSalmonellaorCitrobacter rodentiuminfection, in patients with HIV and in severe acute malnutrition. We recently found that antioxidants allow strict anaerobes, including methanogenic archaea, to thrive in an oxidative environment (aerobic). Here, we tested the metabolomics switching of the 3 most odorous anaerobic microbes isolated from human gut when grown in aerobiosis with antioxidants.

Methods

Three human gut Clostridia,Clostridium sporogenes, Clostridium lituseburenseandClostridium subterminale, isolated by culturomics, were grown in anaerobiosis or in aerobiosis with antioxidants. Gaz and liquid chromatography-Mass spectrometry (GC/MS and LC/MS) were used for metabolomics analysis.

Results

An unexpected global dichotomic metabolomic switching from thiols, alcohols and short-chain fatty acid esters to a specific aerobic metabolic repertoire with the production of alkanes, cycloheptatriene and, paradoxically, increased butyrate production, was observed. Analysis of polar metabolites confirmed the discovery of an unexplored aerobic metabolic repertoire, including the production of specific dipeptides and several lysophospholipids, thus unraveling unsuspected human gut microbiome capacities.

Conclusions

Antioxidants unraveled an unexplored aerobic metabolic repertoire of human gutClostridia. The increased production of butyrate suggests that antioxidants contribute to the maintenance and the active resilience of the human gut microbiome against oxidative aggression, as duringSalmonellainfection.
Microbial dysbiosis and its implications for disease in a genetically depauperate species
Authors: DeCandia Alexandra L. , King Julie L. , vonHoldt Bridgett M.
Published: May 2019

THE host-associated microbiome is increasingly recognized as a critical player in health and immunity. When commensal microbial communities are disrupted, dysbiosis can contribute to disease pathogenesis and severity. Santa Catalina Island foxes (Urocyon littoralis catalinae) present an ideal case study for examining dysbiosis in wildlife due to their depauperate genomic structure and extremely high prevalence of ear canal tumors. Although the precise cause is yet unknown, infection with ear mites (Otodectes cynotis) has been linked to chronic inflammation, which is associated with abnormal cell growth and tumor development. Given the paucity of genomic variation in these foxes, other dimensions of molecular diversity, such as commensal microbes, may be critical to host response and adaptation. We therefore characterized the host-associated microbiome across six body sites of Santa Catalina Island foxes, and performed differential abundance testing between healthy and mite-infected ear canals. We found that mite infection was significantly associated with reduced microbial diversity and evenness, with the opportunistic pathogenStaphylococcus pseudintermediusdominating the ear canal community. These results suggest that secondary bacterial infection may contribute to the sustained inflammation associated with tumor development. Uncovering high abundance ofS. pseudintermediusprovides critical insight into the pathogenesis of this complex system, as the emergence of antibiotic resistant strains remains a concern of the medical, veterinary, and conservation communities. Through use of culture-independent sequencing techniques, this study contributes to the broader effort of applying a more inclusive understanding of molecular diversity to questions within wildlife disease ecology.
Single-cell information analysis reveals small intra- and large intercellular variations increase cellular information capacity
Authors: Wada Takumi , Wataya Mitsutaka , Fujii Masashi , Hironaka Ken-ichi , Eto Miki , Uda Shinsuke , Hoshino Daisuke , Kunida Katsuyuki , Inoue Haruki , Kubota Hiroyuki , Hamaguchi Hiroki , Furuichi Yasuro , Manabe Yasuko , Fujii Nobuharu L. , Kuroda Shinya
Published: May 2019

Cells transmit information about extracellular stimulation through signaling pathways to control cellular function. A signaling pathway can be regarded as a communication channel. In the analysis of channels of cell populations, intercellular variation is considered noise. However, intercellular variation enables individual cells to encode different information. Therefore, at the single-cell level, each cell can be regarded as an independent channel. Thus, we propose that responses of cells of the same type in tissues, such as the fibers in a skeletal muscle, should be regarded as a multiple-cell channel composed of single-cell channels, in which intercellular variation contains information. Here, we applied electrical pulses to individual myotubes from cultured C2C12 cells or dissociated skeletal muscle fibers and measured Ca2+ responses or contraction, respectively, to estimate information capacity in a biological system. For each muscle cell system, we found that a single-cell channel transmitted more information than did a cell-population channel, indicating that the cellular response is consistent with each cell (low intracellular variation) but different among individual cells (high intercellular variation). As cell number and thus the number of single-cell channels increased, a multiple-cell channel transmitted more information by incorporating the differences among individual cells. Thus, a tissue with small intracellular and large intercellular variations has the capacity to distinguish differences in stimulation intensity to precisely control physiological function.

One Sentence Summary

Small intracellular and large intercellular variations increase information transmission for precise control of tissue function.
Associations of ‘Relative corticosterone deficiency’ with genetic variation in CYP17A1 and metabolic syndrome features
Authors: Mackenzie Scott D , Crawford Andrew A , Ackermann Daniel , Schraut Katharina E , Hayward Caroline , Bolton Jennifer L , Saunders Christopher , Al-Dujaili Emad , Dick Bernhard , Escher Geneviève , Vogt Bruno , Pruijm Menno , Ponte Belen , Wilson James F , Strachan Mark W J , Price Jackie F , Phillips David I W , MacKenzie Scott M , Davies Eleanor , Reynolds Rebecca M , Walker Brian R
Published: May 2019

Context and objective

Common genetic variants in CYP17A1 associate with higher blood pressure, putatively from impaired 17α-hydroxylase activity and mineralocorticoid excess. However, the same variants protect against obesity and insulin resistance. We tested whether CYP17A1 variants that enhance 17α-hydroxylase activity cause ‘relative corticosterone deficiency’. Since corticosterone is thought to contribute disproportionately to negative feedback in the hypothalamic-pituitary-adrenal axis, we also tested whether lower corticosterone associates with higher cortisol and hence with metabolic syndrome.

Design

Cross-sectional studies within the population-based Orkney Complex Disease Study (ORCADES; n=2018), VIKING Health Study Shetland (VIKING; n=2098), East Hertfordshire study (EHERTS; n=279), Edinburgh Type 2 Diabetes Study (ET2DS; n=903), and the Swiss Kidney Project on Genes in Hypertension (SKIPOGH; n=888).

Outcome measures

Cortisol and corticosterone in morning plasma samples in ORCADES, VIKING and ET2DS, and in EHERTS in plasma following overnight dexamethasone suppression (0.25mg) and 30 mins after ACTH1-24 (1µg); cortisol and corticosterone metabolites in day and night urine samples in SKIPOGH. Features of the metabolic syndrome including body mass index, systolic blood pressure, lipid profile, fasting glucose, fasting insulin and HOMA-IR.

Results

In ORCADES, ET2DS and SKIPOGH, CYP17A1 variants were associated with corticosterone:cortisol ratio. In ORCADES, VIKING and ET2DS there were consistent associations of morning plasma cortisol and corticosterone with BMI, blood pressure, lipid profile, fasting glucose and HOMA-IR. In EHERTS, however, after dexamethasone suppression and ACTH1-24 stimulation, impaired glucose tolerance and insulin sensitivity were associated with higher cortisol but lower corticosterone. Similarly, in SKIPOGH, low corticosterone:cortisol metabolite ratios were associated with high BMI and dyslipidemia.

Conclusions

‘Relative corticosterone deficiency’, due to a primary alteration in adrenal steroidogenesis favouring cortisol over corticosterone, may mediate the associations of genetic variation in CYP17A1 with metabolic syndrome. However, additional determinants of variation in plasma corticosterone are likely to explain its generally positive associations with features of metabolic syndrome.
Reduced Telomerase Interaction with Telomeres Alters Meiotic Chromosome Motion and Gamete Viability
Authors: Smith Dana L. , Oke Ashwini , Pollard Michael , Anderson Carol M. , Zhuge Tangna , Yam Phoebe , Gromova Tatiana , Conant Kaylynn , Chu Daniel B. , Patel Neem J. , Gonzalez Fernanda , Stoddard Caitlin , Burgess Sean , Hochwagen Andreas , Marshall Wallace F. , Blackburn Elizabeth , Fung Jennifer C.
Published: May 2019

We report a role for telomerase, beyond its known function of telomeric DNA end extension, in maintaining normal chromosome dynamics during meiosis inSaccharomyces cerevisiae.When telomerase at telomeres was reduced by various genetic means, increased frequencies of crossover and noncrossover recombination events occurred. To investigate the mechanism of this increased meiotic recombination, we examined the kinetics of meiosis events, and tracked the movement of chromosomes in live cells during meiotic prophase. Cytoskeletal forces acting on telomeres during meiosis have been shown to promote active chromosome motion needed to pair homologous chromosomes. Here we show that changes in telomerase interaction with telomeres using a tlc1-11 mutant result in altered meiotic motion. Specifically, reduction in telomerase at telomeres leads to a decreased frequency of high velocity chromosome pulls. In the tlc1-11 mutant, we see earlier synapsis and increased genome-wide recombination for the majority of the cells and lower gamete viability. Notably, homologous pairing is not delayed unlike other telomere binding mutants. Although synapsis initiates earlier, the overall timing of synapsis remains the same, except for a subset of cells that do not exit meiosis I. Together, these results suggest that the strong pulling component of the active chromosome motion promotes homolog pairing fidelity, likely by pulling apart improperly associated regions. Our combined observations are consistent with a model in which telomerase-mediated telomeric anchoring to the nuclear envelope helps engage and properly transmit cytoskeletal forces to chromosomes. Thus, telomerase contributes to efficient chromosome movements leading to normal gamete viability.
Cristae undergo continuous cycles of fusion and fission in a MICOS-dependent manner
Authors: Kondadi Arun Kumar , Anand Ruchika , Hänsch Sebastian , Urbach Jennifer , Zobel Thomas , Wolf Dane M. , Segawa Mayuko , Liesa Marc , Shirihai Orian S. , Weidtkamp-Peters Stefanie , Reichert Andreas S.
Published: May 2019

The mitochondrial inner membrane can reshape under different physiological conditions. How and at which frequency this occurs in vivo and what are the molecular players involved is unknown. Here we show using state-of-the-art live-cell stimulated emission depletion (STED) super-resolution nanoscopy that crista junctions (CJs) are dynamically fusing and dividing in a reversible and balanced manner at a timescale of seconds. CJ dynamics is strongly reduced in the absence of the MICOS subunit MIC13. Staining of the cristae membrane using different protein markers or two inner mitochondrial membrane-specific dyes revealed that cristae also undergo continuous cycles of fusion and fission. These processes are dependent on MIC13 and occur at a timescale of seconds, resembling CJ dynamics. Our data further suggest that MIC60 acts as a docking platform pioneering CJ formation. Overall, by employing a variety of advanced imaging techniques including FRAP (Fluorescence-Recovery-After Photobleaching), SPT (Single-Particle-Tracking), live-cell STED and confocal Airyscan microscopy we demonstrate that cristae undergo continuous cycles of fusion and fission in a manner that is mechanistically linked to CJ formation and dynamics.
Two new polymorphic structures of alpha-synuclein solved by cryo-electron microscopy
Authors: Guerrero-Ferreira Ricardo , Taylor Nicholas M.I. , Arteni Ana-Andrea , Kumari Pratibha , Mona Daniel , Ringler Philippe , Britschgi Markus , Lauer Matthias E. , Makky Ali , Verasdock Joeri , Riek Roland , Melki Ronald , Meier Beat H. , Böckmann Anja , Bousset Luc , Stahlberg Henning
Published: May 2019

Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson’s disease (PD). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, respectively. These polymorphs show a radically different structure compared to previously reported polymorphs. The new structures have a 10 nm fibril diameter and are composed of two protofilaments which interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component (NAC) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial PD mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability.

Impact statement

Two new polymorphic structures of recombinant human alpha-synuclein fibrils show striking differences to previous structures, while familial PD mutation sites remain crucial for protofilament interaction and fibril stability.
Large particle fluorescence-activated cell sorting enables high quality single cell RNA-sequencing and functional analysis of adult cardiomyocytes
Authors: Kannan Suraj , Miyamoto Matthew , Lin Brian , Zhu Renjun , Murphy Sean , Kass David , Andersen Peter , Kwon Chulan
Published: May 2019

Rationale

Single cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to profile the transcriptome at single cell resolution, enabling comprehensive analysis of cellular trajectories and heterogeneity during development and disease. However, the use of scRNA-seq remains limited in cardiac pathology owing to technical difficulties associated with the isolation of single adult cardiomyocytes (CMs).

Objective

We investigated the capability of large-particle fluorescence-activated cell sorting (LP-FACS) for isolation of viable single adult CMs.

Methods and Results

We found that LP-FACS readily outperforms conventional FACS for isolation of struturally competent CMs, including large CMs. Additionally, LP-FACS enables isolation of fluorescent CMs from mosaic models. Importantly, the sorted CMs allow generation of high-quality scRNA-seq libraries. Unlike CMs isolated via previously utilized fluidic or manual methods, LP-FAC-isolated CMs generate libraries exhibiting normal levels of mitochondrial transcripts. Moreover, LP-FACS isolated CMs remain functionally competent and can be studied for contractile properties.

Conclusions

Our study enables high quality dissection of adult CM biology at single-cell resolution.
Maternal experience-dependent cortical plasticity in mice is circuit- and stimulus-specific and requires MECP2
Authors: Lau Billy Y. B. , Krishnan Keerthi , Huang Z. Josh , Shea Stephen D.
Published: May 2019

The neurodevelopmental disorder Rett syndrome is caused by mutations in the gene Mecp2. Misexpression of the protein MECP2 is thought to contribute to neuropathology by causing dysregulation of plasticity. Female heterozygous Mecp2 mutants (Mecp2het) failed to acquire a learned maternal retrieval behavior when exposed to pups, an effect linked to disruption of parvalbumin-expressing inhibitory interneurons (PV+) in the auditory cortex. However, the consequences of dysregulated PV+ networks during early maternal experience for auditory cortical sensory activity are unknown. Here we show that maternal experience in wild-type adult female mice (Mecp2wt) triggers suppression of PV+ auditory responses. We also observe concomitant disinhibition of auditory responses in deep-layer pyramidal neurons that is selective for behaviorally-relevant pup vocalizations. These neurons also exhibit sharpened tuning for pup vocalizations following maternal experience. All of these neuronal changes are abolished in Mecp2het, yet a genetic manipulation of GABAergic networks that restores accurate retrieval behavior in Mecp2het also restores maternal experience-dependent plasticity of PV+. Our data are consistent with a growing body of evidence that cortical networks are particularly vulnerable to mutations of Mecp2 in PV+ neurons.
Corrosion performance of mild steel and epoxy coated rebar in concrete under simulated harsh environment
Authors: Sohail Muazzam Ghous , Salih Mohammad , Al Nuaimi Nasser , Kahraman Ramazan
Published: May 2019

Purpose

The purpose of this paper is to present the results of a two-year long study carried out in order to evaluate the corrosion performance of mild steel bare bars (BB) and epoxy-coated rebar (ECR) in concrete under a simulated harsh environment of chlorides.

Design/methodology/approach

The blocks are subjected to Southern Exposure testing. The electrochemical impedance spectroscopy (EIS), linear polarization resistance (LPR) and Tafel plot are performed to measure the polarization resistance and corrosion current densities of these rebars. Knife-peel test was performed to assess the adhesion between epoxy and underlying steel after two years of exposure.

Findings

Mild steel BB showed a high corrosion current density of 1.24 µA/ cm2in Tafel plots and a very low polarization resistance of 4.5 kΩ cm2in LPR technique, whereas very high charge transfer resistance of 1672 and 1675 kΩ cm2is observed on ECR and ECR with controlled damage (ECRCD), through EIS technique, respectively. EIS is observed to be a suitable tool to detect the defects in epoxy coatings. After two years of immersion in 3.89 percent NaCl−solution, the mild steel BB were severely corroded and a considerable weight loss was observed, whereas under heavy chloride attack, ECR showed no deterioration of epoxy coating and neither any corrosion of underlying steel. Results of this study show that the durability of reinforced concrete (RC) structures with respect to corrosion could be enhanced by using ECR, especially in harsh climatic conditions.

Originality/value

The corrosion performance of mild steel and ECR in concrete under a simulating splash zone environment is evaluated. EIS was used to evaluate the health of epoxy and corrosion state of underneath steel rebars. EIS was able to detect the defects in epoxy. The durability of RC structures could be enhanced in harsh climate regions by using ECR.
Cannabis festivals and their attendees in four European cities with different national cannabis policies
Authors: Skliamis Kostas , Korf Dirk J.
Published: May 2019

Purpose

The purpose of this paper is to: describe and contextualize the aims and distinctive and common characteristics of cannabis festivals in countries with different cannabis policies; assess characteristics of participants; identify reasons to attend cannabis festivals; explore to which extent cannabis festivals contribute to the social and cultural acceptance of cannabis, as perceived by attendees.

Design/methodology/approach

The approach incorporates three methods of data collection in the research design; quantitative research among 1,355 participants, participant observation and interviews with the organizers.

Findings

Cannabis festivals in Amsterdam, Berlin, Rome and Athens have common features but also maintain and reproduce local, social and cultural characteristics. Cannabis festivals, as well as their attendees, represent heterogeneous categories. The style of the festival – music festival or march combined with music – affects the main reason for attendance by the participants. In cannabis festivals more similar to music festivals the majority of the respondents attended for entertainment while at the cannabis festivals in the form of a march combined with music the majority attended for protest. Furthermore, increasing age, residency and the high frequency of cannabis use are factors that led the participants to attend for protest.

Originality/value

The research on cannabis festivals is limited. This paper not only explores the aims of cannabis festivals in four capital cities of Europe and the characteristics of their attendees including motivations, but also offers interesting insights for understanding the ways in which political and social constructions like cannabis festivals shape attitudes, perception and behaviors around cannabis use.
The participatory process of planning social and environmental responsibility at a Brazilian university
Authors: Frandoloso Marcos Antonio , Gasparetto Rebelatto Bianca
Published: May 2019

Purpose

Universities have an important role in articulation of the transformation of society, in the formation of individuals capable of acting in the processes that enable sustainable development goals (SDGs), in theoretical areas and in practical and concrete actions. Within the University of Passo Fundo (UPF), Brazil, some practices are being adopted from this perspective. This paper aims to present the efforts of UPF to achieve SDGs in its activities.

Design/methodology/approach

For the development of these research were consulted all administrative instruments of the Foundation University of Passo Fundo, from the proposals and guidelines of its creation in the decade of the 1960s to the most recent of the Institutional Development Plan PDI 2017-2021 and other bibliographic references. From the documentation, the effective results achieved by University Social Responsibility Policy (PRSU) and Institutional Environmental Policy were evaluated.

Findings

A process of consolidating the thematic of the SDGs within the university structure is perceived, with a participatory vision of the academic community.

Research limitations/implications

Although PRSU the policy has been developed since 2005, the effective results are recent and under construction.

Practical implications

The study identified a direction for a change of paradigms, moving from isolated and non-continuity actions to the establishment of normative guidelines.

Social implications

In this sense, this paper seeks to contribute to the process of discussion and generation of practices for the implementation of an agenda with its own goals in the areas of university’s action at local and regional levels, as well as contributing to a wide level.

Originality/value

The paper reports the process of development of the social and environmental policies at UPF to include SDGs in its academic and administrative procedures, which should encourage another similar university to follow suit.
Sustainable development of communities: ISO 37120 and UN goals
Authors: Moschen Suane A. , Macke Janaina , Bebber Suélen , Benetti Correa da Silva Marcelo
Published: May 2019

Purpose

The aims of this study is to put on the agenda discussions concerning the approach of sustainable goals and indicators, in terms of how they relate to each other and how to list their importance within a network of contemporary city management. From the millennium objectives experience, UN has launched the continuity of the development program, through the sustainable development goals (SDG), which have the purpose of giving support to local and regional governments for the 2030 agenda in local sphere. In the city context, sustainable development has also been approached in regulations, like ISO 37120: 2017 “Sustainable development of communities: Indicators for city services and quality of life”. These instruments have in common the concern of offering parameters of public services to citizens and promoting in a uniform manner both social and economic growth of the urban environment.

Design/methodology/approach

The present study aims to compare these two sustainable development tools by means of a documentary analysis and to analyze the feasibility of the proposed indicators and their qualitative evaluation goals to improve citizens’ quality of life.

Findings

The results suggest that the main urban challenges are related to unplanned urban growth and poor-quality public services, which generate a lack of commitment to enforce laws and to achieve sustainable development goals.

Originality/value

The study establishes bases for guiding the discussion to support managers and investors decisions to promote paradigm changes in the citizens’ life and in the way cities are planned.
Challenges and benefits of student sustainability research projects in view of education for sustainability
Authors: Ceulemans Griet , Severijns Nathal
Published: May 2019

Purpose

This paper aims to investigate the educational benefits and challenges of introducing natural science students to on-campus and off-campus sustainability research projects as an approach to education for sustainability.

Design/methodology/approach

The course “Science and Sustainability” at the University of Leuven is a stand-alone course that aims at providing master students in the natural sciences, education for (the benefit of) sustainability action. It was launched in 2016-2017 and has been running for two years now. The first year focused on getting students acquire a similar level of knowledge in sustainability, while, on a higher level, the experiential learning phase (project work) was supported with specific reflection assignments. In the second year, more specific attention was directed toward allowing students to get acquainted with systems thinking and deal with inter- and transdisciplinary issues by approaching problems from a multi-stakeholder view. Insight in the impact and the appreciation of the setup of the course was obtained from a series of questionnaires offered to all participating students at the beginning, about midway, and again at the end of the course.

Findings

Analysis of the students’ self-reported sustainability competence development shows a clear positive impact for almost all students who participated. A clear relation between the observed change and the students’ self-rating and attitude at the start, as well as with their discipline, is observed.

Originality/value

Information is gained on a number of factors of importance to impact the students’ attitude toward action for sustainability, and how this can be further improved.
Engineering education and the development of competencies for sustainability
Authors: Quelhas Osvaldo Luiz Gonçalves , Lima Gilson Brito Alves , Ludolf Nicholas Van-Erven , Meiriño Marcelo Jasmim , Abreu Chrystyane , Anholon Rosley , Vieira Neto Julio , Rodrigues Leandro Silva Goulart
Published: May 2019

Purpose

This paper aims to deal with the skills for sustainable development in engineering courses. The main objective is to identify which competences should be developed in these courses to contribute to the resolution of conflicts related to sustainability, as well as the means used by universities for their development.

Design/methodology/approach

The research is divided into two strands: a theoretical and an empirical one. Concerning the theoretical part, the webibliomining method was adopted, to select the articles that were relevant to the theme, and 22 works were selected. Regarding the empirical study, structured questionnaires were applied to 30 specialists in the field, aiming at validating the competencies found in the literature.

Findings

In the literature, eight main competencies required to the engineering professional, related to sustainability, were found. The empirical study showed that some competences are considered more relevant than others by the interviewees.

Practical implications

The competencies verified in the present study and the relative relevance between them found in the empirical study can contribute to the engineering courses that wish to develop the sustainable behavior of the engineers in their professional or daily life.

Originality/value

The originality of the work consists in presenting to engineering students and teachers as well as professionals of the market and the government the competencies that can contribute to the formation of an engineer capable of bringing adequate solutions to the conflicts of sustainability in the twenty-first century. This paper also presents learning teaching methodologies indicated for this purpose. No other works were found with these results.
Dynamic obstacle-surmounting analysis of a bilateral-wheeled cable-climbing robot for cable-stayed bridges
Authors: Xu Fengyu , Jiang Quansheng
Published: May 2019

Purpose

Field robots can surmount or avoid some obstacles when operating on rough ground. However, cable-climbing robots can only surmount obstacles because their moving path is completely restricted along the cables. This paper aims to analyse the dynamic obstacle-surmounting models for the driving and driven wheels of the climbing mechanism, and design a mechanical structure for a bilateral-wheeled cable-climbing robot to improve the obstacle crossing capability.

Design/methodology/approach

A mechanical structure of the bilateral-wheeled cable-climbing robot is designed in this paper. Then, the kinematic and dynamic obstacle-surmounting of the driven and driving wheels are investigated through static-dynamic analysis and Lagrangian mechanical analysis, respectively. The climbing and obstacle-surmounting experiments are carried out to improve the obstacle crossing capability. The required motion curve, speed and driving moment of the robot during obstacle-surmounting are generated from the experiments results.

Findings

The presented method offers a solution for dynamic obstacle-surmounting analysis of a bilateral-wheeled cable-climbing robot. The simulation, laboratory testing and field experimental results prove that the climbing capability of the robot is near-constant on cables with diameters between 60 and 205 mm.

Originality/value

The dynamic analysis method presented in this paper is found to be applicable to rod structures with large obstacles and improved the stability of the robot at high altitude. Simulations and experiments are also conducted for performance evaluation.
STEM and gender at university: focusing on Irish undergraduate female students’ perceptions
Authors: Kelly Regina , McGarr Oliver , Lehane Louise , Erduran Sibel
Published: May 2019

Purpose

The purpose of this paper is to identify whether or not females believe they associate with the culture of science, technology, engineering and mathematics (STEM) by investigating the perceptions of female students currently enroled in STEM courses.

Design/methodology/approach

The paper presents data from a survey on female STEM students’ “Perspectives of women in STEM”, “Parents’ Science qualification”, “Supports in their STEM Course” and their “Science identify” through a social capital lens. Both qualitative and quantitative methods were used to analyse the data.

Findings

The main findings were that female STEM undergraduates believe social bias, balancing work and family life and lack of role models are the main cause of less women in STEM professions and leadership positions. There were statistically significant differences between how male and female students identified with certain traits, with less females claiming to be intelligent and know about latest discoveries than males.

Research limitations/implications

To eradicate stereotypical views of scientists, it is recommended that Irish higher-education institutions introduce initiatives to increase the socialisation of STEM females within female networks and develop female students’ self-awareness of their own capabilities. The expansion of STEM networks could act as a means to facilitate female students adopting positive science identities, increasing their science capital.

Originality/value

In Ireland, there is a paucity of literature relating to females’ experience of STEM in higher education. This paper provides evidence that despite their engagement with STEM, female undergraduate students subscribe to the stereotypical image of the scientist. This study highlights the need to change the culture experienced by female STEM undergraduates in Ireland so as to improve the experiences and trajectories of women in higher education.