bluuebunny/crossref_metadata_2025_split huggingface dataset:
The membrane microenvironment regulates the sequential attachment of bacteria to host cells
Authors: Pierrat Xavier , Wong Jeremy P.H. , Al-Mayyah Zainebe , Persat Alexandre 
Published: November 2020

AbstractPathogen attachment to host tissue is critical in the progress of many infections. Bacteria use adhesionin vivoto promote colonization and regulate the deployment of contact-dependent virulence traits. To specifically target host cells, they decorate themselves with adhesins, proteins that bind to mammalian cell surface receptors. One common assumption is that adhesin-receptor interactions entirely govern bacterial attachment. However, how adhesins engage with their receptors in anin vivo-like context remains unclear, in particular under the influence of a heterogeneous mechanical microenvironment. We here investigate the biophysical processes governing bacterial adhesion to host cells using a tunable adhesin-receptor system. By dynamically visualizing attachment, we found that bacterial adhesion to host cell surface, unlike adhesion to inert surfaces, involves two consecutive steps. Bacteria initially attach to their host without engaging adhesins. This step lasts about one minute during which bacteria can easily detach. We found that at this stage, the glycocalyx, a layer of glycosylated proteins and lipids, shields the host cell by keeping adhesin away from their receptor ligand. In a second step, adhesins engage with their target receptors to strengthen attachment for minutes to hours. The active properties of the membrane, endowed by the actin cytoskeleton, strengthen specific adhesion. Altogether, our results demonstrate that adhesin-ligand binding is not the sole regulator of bacterial adhesion. In fact, the host cell’s mechanical microenvironment relatively strongly mediated host-bacteria physical interactions, thereby playing an essential role in the onset of infection.
Sand throwing in a pit-building antlion larva from a soil mechanical perspective
Authors: Büsse Sebastian , Büscher Thies H. , Heepe Lars , Gorb Stanislav N. , Stutz Hans Henning 
Published: November 2020

AbstractSandy pitfall traps are an elaborate construction to capture prey and antlions are well-known representatives of this predation technique. From a soil mechanical perspective, antlions exploit the interactions between the particles of their habitat and engineer a stable trap. This construction is close to the unstable state, where a prey item will immediately slide towards the center - towards the ambushing antlion - when accidently entering the trap. This method is efficient, but requires permanent pit maintaining. According to the present knowledge, antlions throw sand at their prey, to distract it, and/or cause sand slides towards the center of the pit. Using sand throwing and escape experiments, as well as finite element analysis, we supported this hypothesis. Furthermore, we added new hypothesis about maintaining the pitfall trap. We showed that sand that accumulates in the center of the pit will be continuously removed, which lead to the slope maintenance close to an unstable condition. This avoids self-burial of the antlion, as well as decreasing the chance of prey item escapes by keeping the slope angle steep. This demonstrates the interaction of an insect larva with its abiotic environment from a novel perspective and adds further insights into longstanding entomological hypotheses.
Automatic identification of bird females using egg phenotype
Authors: Šulc Michal , Hughes Anna E. , Troscianko Jolyon , Štětková Gabriela , Procházka Petr , Požgayová Milica , Piálek Lubomír , Piálková Radka , Brlík Vojtěch , Honza Marcel 
Published: November 2020

AbstractIdentification of individuals greatly contributes to understanding animal ecology and evolution, and in many cases can only be achieved using expensive and invasive techniques. Advances in computing technology offer alternative cost-effective techniques which are less invasive and can discriminate between individuals based on visual and/or acoustic cues. Here, we employ human assessment and an automatic analytical approach to predict the identity of common cuckoo (Cuculus canorus) females based on the appearance of their eggs. The cuckoo’s secretive brood parasitic strategy makes studying its life history very challenging. Eggs were analysed using calibrated digital photography for quantifying spotting pattern, size and shape, and spectrometry for measuring colour. Cuckoo females were identified from genetic sampling of their nestlings, allowing us to determine the accuracy of human and automatic female assignment. Finally, we used a novel ‘same-different’ approach that uses both genetic and phenotypic information to assign eggs that were not genetically analysed.Our results supported the ‘constant egg-type hypothesis’, showing that individual cuckoo females lay eggs with a relatively constant appearance and that eggs laid by different females differ more than eggs laid by the same female. The accuracy of unsupervised hierarchical clustering was comparable to assessments of experienced human observers. Supervised random forest analysis showed better results, with higher cluster accuracy. Same-different analysis was able to assign 22 of 87 unidentified cuckoo eggs to seven already known females.Our study showed that egg appearance on its own is not sufficient for identification of individual cuckoo females. We therefore advocate genetic analysis to be used for this purpose. However, supervised analytical methods reliably assigned a relatively high number of eggs without genetic data to their mothers which can be used in conjunction with genetic testing as a cost-effective method for increasing sample sizes for eggs where genetic samples could not be obtained.
Intronic enhancer region governs transcript-specific BDNF expression in neurons
Authors: Tuvikene Jürgen , Esvald Eli-Eelika , Rähni Annika , Uustalu Kaie , Zhuravskaya Anna , Avarlaid Annela , Makeyev Eugene V. , Timmusk Tõnis 
Published: November 2020

ABSTRACTBrain-derived neurotrophic factor (BDNF) controls the survival, growth, and function of neurons both during the development and in the adult nervous system. BDNF gene is transcribed from several distinct promoters generating transcripts with alternative 5’ exons. BDNF transcripts initiated at the first cluster of exons have been associated with the regulation of body weight and various aspects of social behavior, but the mechanisms driving the expression of these transcripts have remained poorly understood. Here, we identify an evolutionarily conserved intronic enhancer region inside the BDNF gene that regulates both basal and stimulus-dependent expression of the BDNF transcripts starting from the first cluster of 5’ exons in neurons. We further uncover a functional E-box element in the enhancer region, linking the expression of BDNF and various pro-neural basic helix-loop-helix transcription factors. Collectively, our results shed new light on the cell type- and stimulus-specific regulation of the important neurotrophic factor BDNF.
An Epilepsy-Causing Mutation Leads to Co-Translational Misfolding
Authors: Urrutia Janire , Aguado Alejandra , Gomis-Perez Carolina , Muguruza-Montero Arantza , Ballesteros Oscar R. , Zhang Jiaren , Nuñez Eider , Malo Covadonga , Chung Hee Jung , Leonardo Aritz , Bergara Aitor , Villarroel Alvaro 
Published: November 2020

AbstractProtein folding to the native state is particularly relevant in human diseases where inherited mutations lead to structural instability, aggregation and degradation. In general, the amino acid sequence carries all the necessary information for the native conformation, but the vectorial nature of translation can determine the folding outcome. Calmodulin (CaM) recognizes the properly folded Calcium Responsive Domain (CRD) of Kv7.2 channels. Within the IQ motif (helix A), the W344R mutation found in epileptic patients has negligible consequences for the structure of the complex as monitored by multiple in vitro binding assays and molecular dynamic computations. In silico studies revealed two orientations of the side chain, which are differentially populated by WT and W344R variants. Binding to CaM is impaired when the mutated protein is produced in cellulo but not in vitro, suggesting that this mutation impedes proper folding during translation within the cell by forcing the nascent chain to follow a folding route that leads to a non-native configuration, and thereby generating non-functional ion channels that fail to traffic to proper neuronal compartments.
Generating complex patterns of gene expression without regulatory circuits
Authors: Shah Sahil B. , Hill Alexis M. , Wilke Claus O. , Hockenberry Adam J. 
Published: November 2020

AbstractSynthetic biology has successfully advanced our ability to design and implement complex, time-varying genetic circuits to control the expression of recombinant proteins. However, these circuits typically require the production of regulatory genes whose only purpose is to coordinate expression of other genes. When designing very small genetic constructs, such as viral genomes, we may want to avoid introducing such auxiliary gene products while nevertheless encoding complex expression dynamics. To this end, here we demonstrate that varying only the placement and strengths of promoters, terminators, and RNase cleavage sites in a computational model of a bacteriophage genome is sufficient to achieve solutions to a variety of basic gene expression patterns. We discover these genetic solutions by computationally evolving genomes to reproduce desired gene expression time-course data. Our approach shows that non-trivial patterns can be evolved, including complex patterns where the relative ordering of genes by abundance changes over time. We find that some patterns are easier to evolve than others, and comparable expression patterns can be achieved via different genetic architectures. Our work opens up a novel avenue to genome engineering via fine-tuning the balance of gene expression and gene degradation rates.Author summaryViruses that infect bacteria, commonly called bacteriophages, typically have small genomes that encode as few as 10 genes. From the perspective of understanding genome design and regulation, these organisms are important model systems. Similar to cellular species, the genes encoded on a phage genome often must be expressed at different levels and at particular times during the phage lifecycle. Given their unique size constraints, it may be advantageous for phages to accomplish differential gene expression without having to produce a variety of dedicated regulatory molecules—which are frequently encoded on the larger and more complex genomes of free-living species. Here, we use a computational simulation of phage infection coupled with an evolutionary selection algorithm to illustrate that phage genomes can encode complex time-dependent gene expression patterns without the need for dedicated regulatory molecules. We anticipate that this simulation framework may additionally aid future phage genome design and engineering efforts.
Molecular and functional architecture of striatal dopamine release sites
Authors: Banerjee Aditi , Imig Cordelia , Balakrishnan Karthik , Kershberg Lauren , Lipstein Noa , Uronen Riikka-Liisa , Wang Jiexin , Cai Xintong , Benseler Fritz , Rhee Jeong Seop , Cooper Benjamin H. , Liu Changliang , Wojcik Sonja M. , Brose Nils , Kaeser Pascal S. 
Published: November 2020

AbstractDopamine controls striatal circuit function, but its transmission mechanisms are not well understood. We recently showed that dopamine secretion requires RIM, suggesting that it occurs at active zone-like sites similar to conventional synapses. Here, we establish using a systematic conditional gene knockout approach that Munc13 and Liprin-α, active zone proteins for vesicle priming and release site organization, are important for dopamine secretion. Correspondingly, RIM zinc finger and C2B domains, which bind to Munc13 and Liprin-α, respectively, are needed to restore dopamine release in RIM knockout mice. In contrast, and different from conventional synapses, the active zone scaffolds RIM-BP and ELKS, and the RIM domains that bind to them, are expendable. Hence, dopamine release necessitates priming and release site scaffolding by RIM, Munc13, and Liprin-α, but other active zone proteins are dispensable. Our work establishes that molecularly simple but efficient release site architecture mediates fast dopamine exocytosis.
The molecular basis of Kale domestication: Transcription profiling of leaves and meristems provides new insights into the evolution of aBrassica oleraceavegetative morphotype
Authors: Arias Tatiana , Niederhuth Chad , McSteen Paula , Pires J. Chris 
Published: November 2020

ABSTRACTMorphotypes ofBrassica oleraceaare the result of a dynamic interaction between genes that regulate the transition between vegetative and reproductive stages and those that regulate leaf morphology and plant architecture. In kales ornate leaves, delayed flowering, and nutritional quality are some of the characters potentially selected by humans during domestication.We used a combination of developmental studies and transcriptomics to understand the vegetative domestication syndrome of kale. To identify candidate genes that are responsible for the evolution of domestic kale we searched for transcriptome-wide differences among three vegetativeB. oleraceamorphotypes. RNAseq experiments were used to understand the global pattern of expressed genes during one single phase of development in kale, cabbage and the rapid cycling kale line TO1000.We identified gene expression patterns that differ among morphotypes, and estimate the contribution of morphotype-specific gene expression that sets kale apart (3958 differentially expressed genes). Differentially expressed genes that regulate the vegetative to reproductive transition were abundant in all morphotypes. Genes involved in leaf morphology, plan architecture, defense and nutrition were differentially expressed in kale.RNA-Seq experiments allow the discovery of novel candidate genes involved in the kale domestication syndrome. We identified candidate genes differentially expressed in kale that could be responsible for variation in flowering times, taste and herbivore defense, variation in leaf morphology, plant architecture, and nutritional value. Understanding candidate genes responsible for kale domestication is of importance to ultimately improve Cole crop production.
phiC31 integrase for recombination mediated single copy insertion and genome manipulation inC. elegans
Authors: Yang Fang-Jung , Chen Chiao-Nung , Chang Tiffany , Cheng Ting-Wei , Chang Ni-Chen , Kao Chia-Yi , Lee Chih-Chi , Huang Yu-Ching , Chan Shih-Peng , Wang John 
Published: November 2020

AbstractC. elegansbenefits from a large set of tools for genome manipulation. Yet, the insertion of large DNA constructs and the generation of inversions is still challenging. Here, we adapted the phiC31 integrase system forC. elegans.We generated an integrated phiC31 integrase expressing strain flanked by attP sites that also serves as a landing pad for integration of transgenes by recombination mediated cassette exchange (RCME). This strain isunc-119(-)so RMCE integrants can be produced simply by injection of a plasmid carrying attB sites flankingunc-119(+)and the gene(s) of interest. Additionally, phiC31 integrase is removed concomitantly with integration, eliminating the need to outcross away the integrase. Integrations are relatively easy to obtain for insert sizes up to ~15 kb. Taking advantage of this integration method we establish a dual color fluorescent operon reporter system to study post-transcriptional regulation of mRNA. Last we show that large chromosomal segments can be inverted using phiC31 integrase. Thus the phiC31 integrase system should be a useful addition to theC. eleganstoolkit.
Heuristic hyperparameter optimization of deep learning models for genomic prediction
Authors: Han Junjie , Gondro Cedric , Reid Kenneth , Steibel Juan P. 
Published: November 2020

AbstractThere is a growing interest among quantitative geneticists and animal breeders in the use of deep learning (DL) for genomic prediction. However, the performance of DL is affected by hyperparameters that are typically manually set by users. These hyperparameters do not simply specify the architecture of the model, they are also critical for the efficacy of the optimization and model fitting process. To date, most DL approaches used for genomic prediction have concentrated on identifying suitable hyperparameters by exploring discrete options from a subset of the hyperparameter space. Enlarging the hyperparameter optimization search space with continuous hyperparameters is a daunting combinatorial problem. To deal with this problem, we propose using differential evolution (DE) to perform an efficient search of arbitrarily complex hyperparameter spaces in DL models and we apply this to the specific case of genomic prediction of livestock phenotypes. This approach was evaluated on two pig and cattle datasets with real genotypes and simulated phenotypes (N=7,539 animals and M=48,541 markers) and one real dataset (N=910 individuals and M=28,916 markers). Hyperparameters were evaluated using cross validation. We compared the predictive performance of DL models using hyperparameters optimized by DE against DL models with “best practice” hyperparameters selected from published studies and baseline DL models with randomly specified hyperparameters. Optimized models using DE showed clear improvement in predictive performance across all three datasets.DE optimized hyperparameters also resulted in DL models with less overfitting and less variation in predictive performance over repeated retraining compared to non-optimized DL models.
Left frontal motor delta oscillations reflect the temporal integration of multimodal speech
Authors: Biau Emmanuel , Schultz Benjamin G. , Gunter Thomas C. , Kotz Sonja A. 
Published: November 2020

ABSTRACTDuring multimodal speech perception, slow delta oscillations (~1 - 3 Hz) in the listener’s brain synchronize with speech signal, likely reflecting signal decomposition at the service of comprehension. In particular, fluctuations imposed onto the speech amplitude envelope by a speaker’s prosody seem to temporally align with articulatory and body gestures, thus providing two complementary sensations to the speech signal’s temporal structure. Further, endogenous delta oscillations in the left motor cortex align with speech and music beat, suggesting a role in the temporal integration of (quasi)-rhythmic stimulations. We propose that delta activity facilitates the temporal alignment of a listener’s oscillatory activity with the prosodic fluctuations in a speaker’s speech during multimodal speech perception. We recorded EEG responses in an audiovisual synchrony detection task while participants watched videos of a speaker. To test the temporal alignment of visual and auditory prosodic features, we filtered the speech signal to remove verbal content. Results confirm (i) that participants accurately detected audiovisual synchrony, and (ii) greater delta power in left frontal motor regions in response to audiovisual asynchrony. The latter effect correlated with behavioural performance, and (iii) decreased delta-beta coupling in the left frontal motor regions when listeners could not accurately integrate visual and auditory prosodies. Together, these findings suggest that endogenous delta oscillations align fluctuating prosodic information conveyed by distinct sensory modalities onto a common temporal organisation in multimodal speech perception.
Basal ganglia and cerebellar contributions to vocal emotion processing: a high resolution fMRI study
Authors: Ceravolo Leonardo , Frühholz Sascha , Pierce Jordan , Grandjean Didier , Péron Julie 
Published: November 2020

AbstractUntil recently, brain networks underlying emotional voice prosody decoding and processing were focused on modulations in primary and secondary auditory, ventral frontal and prefrontal cortices, and the amygdala. Growing interest for a specific role of the basal ganglia and cerebellum was recently brought into the spotlight. In the present study, we aimed at characterizing the role of such subcortical brain regions in vocal emotion processing, at the level of both brain activation and functional and effective connectivity, using high resolution functional magnetic resonance imaging. Variance explained by low-level acoustic parameters (fundamental frequency, voice energy) was also modelled. Wholebrain data revealed expected contributions of the temporal and frontal cortices, basal ganglia and cerebellum to vocal emotion processing, while functional connectivity analyses highlighted correlations between basal ganglia and cerebellum, especially for angry voices. Seed-to-seed and seed-to-voxel effective connectivity revealed direct connections within the basal ganglia ̶ especially between the putamen and external globus pallidus ̶ and between the subthalamic nucleus and the cerebellum. Our results speak in favour of crucial contributions of the basal ganglia, especially the putamen, external globus pallidus and subthalamic nucleus, and several cerebellar lobules and nuclei for an efficient decoding of and response to vocal emotions.
Why should broadband be free? Promises and rhetoric in the United Kingdom general election of 2019
Authors: Sutherland Ewan 
Published: November 2020

Purpose
This paper aims to analyse the promises of the various political party in the 2019 general election in the United Kingdom (UK) concerning the provision of broadband, especially in remote and rural areas.

Design/methodology/approach
This is an analysis of the party manifestos, some interviews and speeches involving party leaders. It identified the various commitments, any costs for those and the reasoning given.

Findings
The UK lags badly on fibre to the premises, both homes and offices. Without analysing the reasons, the two dominant parties proposed to borrow large amounts of money to fund fibre deployment, the Conservative Party without explaining how it would be disbursed. The Labour Party produced a confused proposal to nationalise BT Openreach and probably other operators, without explaining how this transition would work. Nor did they explain why the service was to be free to users.

Practical implications
The UK political parties need to improve their understanding of broadband and digital policies, including means to simplify the governance of markets.

Originality/value
This is the first analysis of the broadband commitments of a UK general election and one of the very few analyses of political offers in an election.