bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic background and habitat drive the genetic diversification ofEscherichia coli
Authors: Touchon Marie , Perrin Amandine , de Sousa Jorge André Moura , Vangchhia Belinda , Burn Samantha , O’Brien Claire L. , Denamur Erick , Gordon David , Rocha Eduardo PC 
Published: February 2020

AbstractEscherichia coliis a commensal of birds and mammals, including humans. It can act as an opportunistic pathogen and is also found in water and sediments. Since most population studies have focused on clinical isolates, we studied the phylogeny, genetic diversification, and habitat-association of 1,294 isolates representative of the phylogenetic diversity of more than 5,000, mostly non-clinical, isolates originating from humans, poultry, wild animals and water sampled from the Australian continent. These strains represent the species diversity and show large variations in gene repertoires within sequence types. Recent gene transfer is driven by mobile elements and determined by habitat sharing and by phylogroup membership, suggesting that gene flow reinforces the association of certain genetic backgrounds with specific habitats. The phylogroups with smallest genomes had the highest rates of gene repertoire diversification and fewer but more diverse mobile genetic elements, suggesting that smaller genomes are associated with higher, not lower, turnover of genetic information. Many of these small genomes were in freshwater isolates suggesting that some lineages are specifically adapted to this environment. Altogether, these data contribute to explain why epidemiological clones tend to emerge from specific phylogenetic groups in the presence of pervasive horizontal gene transfer across the species.
A cerebellar internal model calibrates a feedback controller involved in sensorimotor control
Authors: Markov Daniil A. , Petrucco Luigi , Kist Andreas M. , Portugues Ruben 
Published: February 2020

AbstractAnimals must adapt their behavior to survive in a changing environment. Behavioral adaptations can be evoked by two mechanisms: feedback control and internal-model-based control. Feedback controllers can maintain the sensory state of the animal at a desired level under different environmental conditions. In turn, internal models learn the relationship between behavior and resulting sensory consequences in order to modify the behavior when this relationship changes. Here, we present multiple perturbations in visual feedback to larval zebrafish performing the optomotor response and show that they react to these perturbations through a feedback control mechanism. In contrast, if a perturbation is long-lasting, fish adapt their behavior by updating a cerebellum-dependent internal model. We use modelling and functional imaging to show that neuronal requirements for these mechanisms are met in the larval zebrafish brain. Our results illustrate the role of the cerebellum in encoding internal models and how these can calibrate neuronal circuits involved in reactive behaviors depending on the interactions between animal and environment.HighlightsBehavioral reactions to unexpected changes in visual feedback are implemented by a feedback control mechanismA long-lasting change in visual feedback updates the state of the neuronal controllerThe cerebellar internal model mediates this recalibration
Alzheimer’s disease-relevant tau modifications selectively impact neurodegeneration and mitophagy in a novelC. eleganssingle-copy transgenic model
Authors: Guha Sanjib , Fischer Sarah , Johnson Gail VW , Nehrke Keith 
Published: February 2020

ABSTRACTBackgroundA defining pathological hallmark of the progressive neurodegenerative disorder Alzheimer’s disease (AD) is the accumulation of misfolded tau with abnormal post-translational modifications (PTMs). These include phosphorylation at Threonine 231 (T231) and acetylation at Lysine 274 (K274) and at Lysine 281 (K281). Although tau is recognized to play a central role in pathogenesis of AD, the precise mechanisms by which these abnormal PTMs contribute to the neural toxicity of tau is unclear.MethodsHuman 0N4R tau (wild type) was expressed in touch receptor neurons of the genetic model organismC. elegansthrough single-copy gene insertion. Defined mutations were then introduced into the single-copy tau transgene through CRISPR-Cas9 genome editing. These mutations included T231E and T231A, to mimic phosphorylation and phospho-ablation of a commonly observed pathological epitope, respectively, and K274/281Q, to mimic disease-associated lysine acetylation. Stereotypical touch response assays were used to assess behavioral defects in the transgenic strains as a function of age, and genetically-encoded fluorescent biosensors were used to measure the morphological dynamics and turnover of touch neuron mitochondria.ResultsUnlike existing tau overexpression models,C. eleganssingle-copy expression of tau did not elicit overt pathological phenotypes at baseline. However, strains expressing disease associated PTM-mimetics (T231E and K274/281Q) exhibited reduced touch sensation and morphological abnormalities that increased with age. In addition, the PTM-mimetic mutants lacked the ability to engage mitophagy in response to mitochondrial stress.ConclusionsLimiting the expression of tau results in a genetic model where pathological modifications and age result in evolving phenotypes, which may more closely resemble the normal progression of AD. The finding that disease-associated PTMs suppress compensatory responses to mitochondrial stress provides a new perspective into the pathogenic mechanisms underlying AD.
Single exposure to social defeat or immobilization stress fails to induce lasting alterations in general anxiety and hippocampal neurogenesis in Wistar and wild-type Groningen rats
Authors: Patel Deepika , Koutlas Ioannis , de Waard Sebastiaan H. , Buwalda Bauke 
Published: February 2020

ABSTRACTSuppression of hippocampal neurogenesis is a readout for stress-induced alterations in neuroplasticity. In this study, we hypothesized that a single episode of severe social or non-social stress would differentially suppress neurogenesis in the dentate gyrus (DG) 10 days later in two rat strains. We anticipated that the suppression following social stress would be less severe in wildtype Groningen (WTG) rats, a rat strain considered relatively resilient to social stressors. Male Wistar and WTG were subjected to either social defeat or to immobilization stress. Behavioral response to social defeat and acute corticosterone response to both stressors was measured as well as anxiety behavior 10 days later on the elevated plus maze. Subsequently, brains were collected following cardiac aldehyde perfusion. The behavioral freezing response to defeat was much stronger in Wistar rats as compared to WTG rats. Acute corticosteroid response was similar in both strains although Wistar rats more rapidly resumed baseline values. There was no significant effect of both stressors on hippocampal DG cell proliferation and differentiation as well as on anxiety behavior. However, a striking strain difference appeared in anxiety behavior and both markers of neurogenesis. The WTG strain exhibiting much lower anxiety as well as reduced rate of hippocampal neurogenesis under all treatments. The results in this study suggest that both short-lasting acute stressors failed to induce lasting anxiety or decreased neurogenesis in the DG. Future studies could explore if and how rate of hippocampal neurogenesis is related with behavioral coping with stress.
Competitive binding of independent extension and retraction motors explains the quantitative dynamics of type IV pili
Authors: Koch Matthias D. , Fei Chenyi , Wingreen Ned S. , Shaevitz Joshua W. , Gitai Zemer 
Published: February 2020

AbstractThe functions of type IV pili (TFP) are mediated by cycles of extension and retraction. The coordination of these cycles remains mysterious due to poor quantification of TFP dynamics. Here we fluorescently label the TFP in the opportunistic pathogenPseudomonas aeruginosaand track the full extension and retraction cycles of individual TFP to quantify their dynamics. We test several models for the switch between extension and retraction using quantitative experiments, biophysical modeling and genetics. We invalidate the prominent hypothesis that this switch is triggered by surface contact. Instead, we show that the entire repetitive cycle of extension and retraction of individual TFP is governed by the stochastic binding of antagonistic extension and retraction motors and explain how this mechanism quantitatively defines physiologically-important features like TFP length and their production rate. Interestingly, our results suggest that the major throttle of TFP production is the unbinding of the retraction motor.
DeepTracer: Predicting Backbone Atomic Structure from High Resolution Cryo-EM Density Maps of Protein Complexes
Authors: Pfab Jonas , Si Dong 
Published: February 2020

AbstractMotivationAccurately determining the atomic structure of proteins represents a fundamental problem in the field of structural bioinformatics. A solution would be significant as protein structure information could be utilized in the medical field, e.g. in the development of vaccines for new viruses. This paper focuses on predicting the protein structure based on 3D images of the proteins captured through cryogenic electron microscopes (cryo-EM). A fully automated computationally efficient protein structure prediction method would be particularly beneficial in the field of cryo-EM as the technology allows researchers to photograph multiple large protein complexes in a single study, which means that a fast prediction method could allow for a high throughput of derived protein structures. We present a deep learning approach, DeepTracer, for predicting locations of the backbone atoms, secondary structure elements, and the amino acid types. In order to connect the predicted amino acids into chains, we applied a modified traveling salesman algorithm.ResultsWe trained our deep learning model on experimental cryo-EM density maps and tested it on a set of 50 density maps. We found that our new approach predicted protein structures with an average RMSD value of 1.18 and a coverage of 87.5%. Furthermore, we detected secondary structure information for 87.2% of amino acids correctly. We also showed preliminarily that 25.2% of amino acid types could be predicted directly from the 3D cryo-EM density map, considering 20 different types in total. Finally, we noted that the prediction runtime of DeepTracer is significantly improved compared to other methods. It predicts a large protein complex structure of more than 30,000 amino acids in only 2 hours.AvailabilityThe repository of this project will be published.Contactdongsi@uw.eduSupplementary informationSupplementary data will be available atBioinformaticsonline.
Rice Bran and Quercetin Produce a Positive Synergistic Effect on Human Gut Microbiota, Elevate the Level of Propionate, and Reduce the Population ofEnterobacteriaceaefamily when Determined using a Bioreactor Model
Authors: Ghimire Sudeep , Wongkuna Supapit , Sankaranarayanan Ranjini , Ryan Elizabeth P. , Bhat G. Jayarama , Scaria Joy 
Published: February 2020

AbstractDiet is one of the prominent determinants of gut microbiota composition significantly impacting human health. Recent studies with dietary supplements such as rice bran and quercetin have been shown to provide a beneficial impact on the host by positively influencing the gut microbiota. However, the specific bacterial species impacted when rice bran or quercetin is present in the diet is not well understood. Therefore, in this study, we used a minibioreactor array system as a model to determine the effect of quercetin and rice bran individually, as well as in combination, on gut microbiota without the confounding host factors. We found that rice bran exerts higher shift in gut microbiome composition when compared to quercetin. At the species level,Acidaminococcus intestiniwas the only significantly enriched taxa when quercetin was supplemented, while 15 species were enriched in rice bran supplementation and 13 were enriched when quercetin and rice bran were supplemented in combination. When comparing the short chain fatty acid production, quercetin supplementation significantly enriched isobutyrate production while propionate dominated the quercetin and rice bran combined group. Higher levels of propionate were highly correlated to the lower abundance of the potentially pathogenicEnterobacteriaceaefamily. These findings suggest that the combination of rice bran and quercetin serve to enrich beneficial bacteria and reduce potential opportunistic pathogens. However, furtherin vivostudies are necessary to determine the synergistic effect of rice bran and quercetin on host health and immunity.ImportanceRice bran and quercetin are dietary components that shape host health by interacting with the gut microbiome. Both these substrates have been reported to provide nutritional and immunological benefits individually. However, considering the complexity of the human diet, it is useful to determine how the combination of food ingredients such as rice bran and quercetin influences the human gut microbiota. Our study provides insights into how these ingredients influence microbiome composition alone and in combinationin vitro. This will allow us to identify which species in the gut microbiome are responsible for biotransformation of these dietary ingredients.. Such information is helpful for the development of synbiotics to improve gut health and immunity.
Endocrine fine-tuning of daily locomotor activity patterns under non-starving conditions in Drosophila
Authors: Pauls Dennis , Selcho Mareike , Räderscheidt Johanna , Amatobi Kelechi M. , Fekete Agnes , Krischke Markus , Hermann-Luibl Christiane , Ünal Ayten Gizem , Ehmann Nadine , Itskov Pavel M. , Helfrich-Förster Charlotte , Kühnlein Ronald P. , Mueller Martin J. , Wegener Christian 
Published: February 2020

1.AbstractAnimals need to balance competitive behaviours to maintain internal homeostasis. The underlying mechanisms are complex, but typically involve neuroendocrine signalling. UsingDrosophila, we systematically manipulated signalling between energy-mobilising endocrine cells producing adipokinetic hormone (AKH), octopaminergic neurons and the energy-storing fat body to assess whether this neuroendocrine axis involved in starvation-induced hyperactivity also balances activity levels underad libitumaccess to food.Our results suggest that AKH signals via two divergent pathways that are mutually competitive in terms of activity and rest. AKH increases activity via the octopaminergic system during the day, while it prevents high activity levels during the night by signalling to the fat body. This regulation involves feedback signalling from octopaminergic neurons to AKH-producing cells (APCs). APCs are known to integrate a multitude of metabolic and endocrine signals. Our results add a new facet to the versatile regulatory functions of APCs by showing that their output contributes to shape the daily activity pattern underad libitumaccess to food.
A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission
Authors: Balestra Aurélia C , Zeeshan Mohammad , Rea Edward , Pasquarello Carla , Brusini Lorenzo , Mourier Tobias , Subudhi Amit Kumar , Jemelin Natacha Klages , Arboit Patrizia , Pandey Rajan , Brady Declan , Vaughan Sue , Holder Anthony A , Pain Arnab , Ferguson David J P , Hainard Alexandre , Tewari Rita , Brochet Mathieu 
Published: February 2020

SummaryCell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. We show thatPlasmodium bergheiCDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission. It phosphorylates canonical CDK motifs of components in the pre-replicative complex and is essential for DNA replication. During a replicative cycle, CRK5 stably interacts with a singlePlasmodium-specific cyclin (SOC2), although we obtained no evidence of SOC2 cycling by transcription, translation or degradation. Our results provide evidence that duringPlasmodiummale gametogony, this divergent cyclin/CDK pair fills the functional space of other eukaryotic cell-cycle kinases controlling DNA replication.
Separation of newly replicated bacterial chromosomes: the role ofEscherichia coliTopoisomerase IV
Authors: Helgesen Emily , Sætre Frank , Skarstad Kirsten 
Published: February 2020

AbstractTopoisomerase IV (TopoIV) is a vital bacterial enzyme which disentangles newly replicated DNA and enables segregation of daughter chromosomes. In bacteria, DNA replication and segregation are concurrent processes. This means that TopoIV must continually remove inter-DNA linkages during replication. There exists a short time lag of about 5-10 minutes between replication and segregation in which the daughter chromosomes are intertwined. Exactly where TopoIV binds during the cell cycle has been the subject of much debate. We show here that TopoIV localizes to the origin proximal side of the fork trailing protein SeqA and follows the movement pattern of the replication machinery in the cell.
Overexpression of sedoheptulose-1,7-bisphosphatase enhances photosynthesis inChlamydomonas reinhardtiiand has no effect on the abundance of other Calvin-Benson cycle enzymes
Authors: Hammel Alexander , Sommer Frederik , Zimmer David , Stitt Mark , Mühlhaus Timo , Schroda Michael 
Published: February 2020

AbstractThe productivity of plants and microalgae needs to be increased to feed the growing world population and to promote the development of a low-carbon economy. This goal can be achieved by improving photosynthesis via genetic engineering. In this study, we have employed the Modular Cloning strategy to overexpress the Calvin-Benson cycle (CBC) enzyme sedoheptulose-1,7 bisphosphatase (SBP1) up to 3-fold in the unicellular green algaChlamydomonas reinhardtii. The protein derived from the nuclear transgene represented ∼0.3% of total cell protein. Photosynthetic rate and growth were significantly increased in SBP1-overexpressing lines under high-light and high-CO2conditions. Absolute quantification of the abundance of all other CBC enzymes by the QconCAT approach revealed no consistent differences between SBP1-overexpressing lines and the recipient strain. This analysis also revealed that the eleven CBC enzymes represent 11.9% of total cell protein inChlamydomonas. Here the range of concentrations of CBC enzymes turned out to be much larger than estimated earlier, with a 128-fold difference between the most abundant CBC protein (rbcL) and the least abundant (triose phosphate isomerase). Accordingly, the concentrations of the CBC intermediates are often but not always higher than the binding site concentrations of the enzymes for which they act as substrates. The enzymes with highest substrate to binding site ratios might represent good candidates for overexpression in subsequent engineering steps.
Lean Six Sigma and quality frameworks in higher education – a review of literature
Authors: Davidson Janelle Margaret , Price Oriana Milani , Pepper Matthew 
Published: February 2020

Purpose
This paper aims to present a review of literature that considers the use of quality frameworks in higher education (HE). Quality frameworks provide a minimum standard of teaching and learning of students. This systematic literature review identifies the tools and techniques to continuously improve the systems and processes that underpin teaching and learning are missing. With this in mind, the authors present a focus on Lean Six Sigma (LSS) as an improvement methodology adopted by the HE sector and present the factors that drive or hinder the implementation of LSS in higher education institutions (HEIs).

Design/methodology/approach
A review of the literature and thematic analysis has been undertaken relating to the application of quality frameworks and methodologies within the literature set.

Findings
The findings show that quality frameworks to be lacking insofar as their focus on compliance is no incentive for continuous improvement. This finding is not unique to the HEI sector and similar challenges exist in other sectors. A further finding identifies the need for academic professional practice to go beyond quality assurance to attend to the transformation of students. Together these present an apparent disconnect between continuous improvement methodology and HE quality frameworks.

Research limitations/implications
A literature review does have limitations insofar as some literature may have been missed because of different key terms. A further consideration being literature from 2019 not available at the time the review was conducted.

Practical implications
It represents the state of play in regard to the use of quality frameworks operating in HE and business schools. Insight is offered into how the use of continuous improvement methods can deliver quality in HE to benefit the sector, students and others. An agenda for future research is offered.

Originality/value
The discussion is valuable as it seeks to improve understanding of the relationships between methodologies with adopted quality frameworks in the HEI sector. A contribution is made in the use of force field analysis to represent the critical success factors and barriers of LSS in HEI.
The impact of patient recovery flexibility on service experience in public healthcare
Authors: Kumar Pradeep 
Published: February 2020

Purpose
This study aims to identify the dimensions of patient recovery flexibility in the public healthcare context and its impact on the service experience. The study also explores the strategies and contextual influences to attain patient recovery flexibility.

Design/methodology/approach
This paper uses a case study method based on a semi-structured interview with healthcare professionals, observations and informal discussions.

Findings
In the present study, several dimensions of patient recovery flexibility are reported. Different internal and external strategies to exhibit patient recovery flexibility, as well as two contextual influences, are identified. An integrative framework is developed to establish the relationship of patient recovery flexibility with service experience in public healthcare.

Research limitations/implications
The study was conducted in a public healthcare setting in India. The sample size for the semi-structured interview was limited to healthcare professionals, and the patient’s perspective is missing.

Originality/value
This paper contributes to the growing need for patient recovery flexibility as a strategy in the public healthcare delivery system. It offers new insights to address the gap in the literature regarding the linkage of patient recovery flexibility and service experience. The study provides an integrative framework of dimensions of patient recovery flexibility, strategies, contextual influences and the impact on the service experience. The framework and propositions presented in the study will guide future research that is needed in this area. This study provides an overview to shape and redesign the after-service support from a flexibility perspective in public healthcare for the improved service experience.