bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type IV pili share a conserved mechanism of motor-independent retraction that is an inherent property of the pilus filament
Authors: Chlebek Jennifer L. , Craig Lisa , Dalia Ankur B. 
Published: February 2021

ABSTRACTType IV pili (T4P) are dynamic surface appendages that promote virulence, biofilm formation, horizontal gene transfer, and motility in diverse bacterial species. Pilus dynamic activity is best characterized in T4P that use distinct ATPase motors for pilus extension and retraction. Many T4P systems, however, lack a dedicated retraction motor and the mechanism underlying this motor-independent retraction remains a mystery. Using theVibrio choleraecompetence pilus as a model system, we identify mutations in the major pilin gene that enhance motor-independent retraction. These mutants produced less stable pili, likely due to diminished pilin-pilin interactions within the filament. One mutation adds a bulky residue to α1C, a universally conserved feature of type IV pilins. We found that inserting a bulky residue into α1C of the retraction motor-dependentAcinetobacter baylyicom-petence T4P is sufficient to induce motor-independent retraction. Conversely, removing bulky residues from α1C of the retraction motor-independentV. choleraetoxin-co-regulated T4P stabilizes the filament and prevents retraction. Furthermore, alignment of pilins from the broader type IV filament (T4F) family indicated that retraction motor-independent T4P, Com pili, and type II secretion systems generally encode larger residues within α1C oriented toward the pilus core compared to retraction motor-dependent T4P. Together, our data demonstrate that motor-independent retraction relies on the inherent instability of the pilus filament that may be conserved in diverse T4Fs. This provides the first evidence for a long-standing, yet untested, model in which pili retract in the absence of a motor by spontaneous de-polymerization.SIGNIFICANCEExtracellular pilus filaments are critical for the virulence and persistence of many bacterial pathogens. A crucial property of these filaments is their ability to dynamically extend and retract from the bacterial surface. A detailed mechanistic understanding of pilus retraction, however, remains lacking in many systems. Here, we reveal that pilus retraction is an inherent property of the pilus filament. These observations are broadly relevant to diverse pilus systems, including those in many bacterial pathogens, and may help inform novel therapeutic strategies that aim to target pilus dynamic activity.
Connectivity patterns that shape olfactory representation in a mushroom body network model
Authors: Zavitz Daniel , Amematsro Elom A. , Borisyuk Alla , Caron Sophie J.C. 
Published: February 2021

ABSTRACTCerebellum-like structures — such as the insect mushroom body — are found in many brains and share a basic fan-out–fan-in network architecture. How the specific structural features of these networks give rise to their learning function remains largely unknown. To investigate this structure–function relationship, we developed a minimal computational model of the extensively studied Drosophila melanogaster mushroom body. We show how well-defined connectivity patterns between the Kenyon cells — the constituent neurons of the mushroom body — and their input projection neurons endow different functions, enabling the mushroom body to process olfactory information more efficiently. First, biases in the likelihoods at which individual projection neurons connect to Kenyon cells allow the mushroom body to prioritize the learning of particular, ethologically meaningful odors. Second, groups of projection neurons connecting preferentially to the same Kenyon cells facilitate the mushroom body to generalize across similar odors. Altogether, our results demonstrate how different connectivity patterns shape the representation space of a well-studied cerebellum-like network and impact its learning outcomes.
Ultra-sensitive nanoLC-MS of sub nanogram protein samples using second generation micro pillar array LC technology with Orbitrap Exploris 480 and FAIMS PRO
Authors: Stejskal Karel , de Beeck Jeff Op , Dürnberger Gerhard , Jacobs Paul , Mechtler Karl 
Published: February 2021

ABSTRACTIn the light of the ongoing single-cell revolution, scientific disciplines are combining forces to retrieve as much relevant data as possible from trace amounts of biological material. For single cell proteomics, this implies optimizing the entire workflow from initial cell isolation down to sample preparation, liquid chromatography (LC) separation, mass spectrometer (MS) data acquisition and data analysis. To demonstrate the potential for single cell and limited sample proteomics, we report on a series of benchmarking experiments where we combine LC separation on a new generation of micro pillar array columns with state-of-the-art Orbitrap MS/MS detection and High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS). This dedicated limited sample column has a reduced cross section and micro pillar dimensions that have been further downscaled (inter pillar distance and pillar diameter by a factor of 2), resulting in improved chromatography at reduced void times. A dilution series of a HeLa tryptic digest (5-0.05 ng/μL) was used to explore the sensitivity that can be achieved. Comparative processing of the MS/MS data with Sequest HT, MS Amanda, Mascot and SpectroMine pointed out the benefits of using Sequest HT together with INFERYS when analyzing sample amounts below 1 ng. 2855 protein groups were identified from just 1 ng of HeLa tryptic digest hereby increasing detection sensitivity as compared to a previous contribution by a factor well above 10. By successfully identifying 1486 protein groups from as little as 250 pg of HeLa tryptic digest, we demonstrate outstanding sensitivity with great promise for use in limited sample proteomics workflows.
Synthetic multistability in mammalian cells
Authors: Zhu Ronghui , del Rio-Salgado Jesus M. , Garcia-Ojalvo Jordi , Elowitz Michael B. 
Published: February 2021

AbstractIn multicellular organisms, gene regulatory circuits generate thousands of molecularly distinct, mitotically heritable states, through the property of multistability. Designing synthetic multistable circuits would provide insight into natural cell fate control circuit architectures and allow engineering of multicellular programs that require interactions among cells in distinct states. Here we introduce MultiFate, a naturally-inspired, synthetic circuit that supports long-term, controllable, and expandable multistability in mammalian cells. MultiFate uses engineered zinc finger transcription factors that transcriptionally self-activate as homodimers and mutually inhibit one another through heterodimerization. Using model-based design, we engineered MultiFate circuits that generate up to seven states, each stable for at least 18 days. MultiFate permits controlled state-switching and modulation of state stability through external inputs, and can be easily expanded with additional transcription factors. Together, these results provide a foundation for engineering multicellular behaviors in mammalian cells.
A new type of mouse gaze shift is led by directed saccades
Authors: Zahler Sebastian H. , Taylor David E. , Wong Joey Y. , Adams Julia M. , Feinberg Evan H. 
Published: February 2021

AbstractAnimals investigate their environments by directing their gaze towards salient stimuli. In the prevailing view, mouse gaze shifts are led by head rotations that trigger compensatory, brainstem-mediated eye movements, including saccades to reset the eyes. These “recentering” saccades are attributed to head movement-related vestibular and optokinetic cues. However, microstimulating mouse superior colliculus (SC) elicits directed head and eye movements that resemble SC-dependent sensory-guided gaze shifts made by other species, raising the possibility mice generate additional types of gaze shifts. We investigated this possibility by tracking eye and attempted head movements in a head-fixed preparation that eliminates head movement-related sensory cues. We found tactile stimuli evoke gaze shifts involving directed saccades that precede attempted head rotations. Optogenetic perturbations revealed SC drives touch-evoked gaze shifts. Thus, mice make sensory-guided, SC-dependent gaze shifts led by directed saccades. Our findings uncover diversity in mouse gaze shifts and provide a foundation for studying head-eye coupling.
Participant followup rate can bias structural imaging measures in longitudinal studies
Authors: Beare Richard , Ball Gareth , Yang Joseph Yuan-Mou , Moran Chris , Srikanth Velandai , Seal Marc ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2021

AbstractLongitudinal MRI analysis is essential to accurately describe neuroanatomical changes over time. Loss of participants to followup (dropout) in longitudinal studies is inevitable and can lead to great difficulty in interpretation of statistical results if dropout is correlated with a study outcome or exposure. Beyond this, technical aspects of longitudinal MRI analysis require specialised processing pipelines to improve reliability while avoiding bias towards individual timepoints. In this article we test whether there is an additional problem that must be considered in longitudinal imaging studies, namely whether dropout has an impact on the function of FreeSurfer, a popular software pipeline used to estimate important structural brain metrics.We find that the number of acquisitions available per individual can impact the estimation of cortical thickness and brain volume using the FreeSurfer longitudinal pipeline, and can induce group differences in brain metrics. The effect on trajectories of brain metrics is smaller than the effect on brain metrics.HighlightsLongitudinal MRI analysis is essential to accurately track neuroanatomical changes over timeLongitudinal MRI analysis requires specialised processing pipelines to reduce bias towards single timepointsParticipant drop out or loss can bias neuroanatomical measures derived from longitudinal pipelinesWe find that group differences in the number of acquisitions available to analyse can cause group differences in estimated cortical thickness and brain volumeThis bias appears to be due to the number of scans used to create individualised templates in the Freesurfer longitudinal pipelineThe effect on estimates of brain metric trajectories appears smaller than the effect on the estimates of brain metrics
5-hydroxymethylcytosine mediated active demethylation is required for neuronal differentiation and function
Authors: Stoyanova Elitsa , Riad Michael , Rao Anjana , Heintz Nathaniel 
Published: February 2021

SUMMARYAlthough high levels of 5-hydroxymethylcytosine (5hmC) accumulate in neurons, it is not known whether 5hmC can serve as an intermediate in DNA demethylation in postmitotic neurons. We report high resolution mapping of DNA methylation and hydroxymethylation, chromatin accessibility, and histone marks in developing postmitotic Purkinje cells (PCs). Our data reveal new relationships between PC transcriptional and epigenetic programs, and identify a class of genes that lose both 5mC and 5hmC during terminal differentiation. Deletion of the 5hmC writers Tet1, Tet2, and Tet3 from postmitotic PCs prevents loss of 5mC and 5hmC in regulatory domains and gene bodies and hinders transcriptional and epigenetic developmental transitions, resulting in hyper-excitability and increased susceptibility to excitotoxic drugs. Our data demonstrate that Tet-mediated active DNA demethylation occurs in vivo, and that acquisition of the precise molecular and electrophysiological properties of adult PCs requires continued oxidation of 5mC to 5hmC during the final phases of differentiation.
A Framework for Sensor-based Assessment of Upper-limb Functioning
Authors: David Ann , Subash Tanya , Varadhan SKM , Melendez-Calderon Alejandro , Balasubramanian Sivakumar 
Published: February 2021

AbstractThe ultimate goal of any upper-limb neurorehabilitation procedure is to improve upper-limb functioning in daily life. While clinic-based assessments provide an assessment of what a patient can do, they do not completely reflect what a patient does in his/her daily life. The compensatory use of the less affected upper-limb (e.g. “learned non-use”) in daily life is a common behavioral pattern seen in patients with hemiparesis. To this end, there has been an increasing interest in the use of wearable sensors to objectively assess upper-limb functioning. This paper presents a framework for assessing upper-limb functioning using sensors by providing: (a) a set of definitions of important construct associated with upper-limb functioning; (b) presenting different visualization methods for evaluating upper-limb functioning, along ways to qualitatively analyze different visualization methods; and (c) two new measures for quantifying how much an upper-limb is used and the relative bias in the use of the two upper-limbs. The demonstration of some of these components is presented using data collected from inertial measurement units from a previous study. The proposed framework can help guide the future technical and clinical work in this area to realize a valid, objective, and robust tool for assessing upper-limb functioning. This will in turn drive the refinement and standardization of the assessment of upper-limb functioning.
An Activator Locks Kv7.1 Channels Open by Electro-Mechanical Uncoupling and Allosterically Modulates its Pore
Authors: Möller Melina , Schreiber Julian A. , Zaydman Mark , Beller Zachary , Becker Sebastian , Ritter Nadine , Wrobel Eva , Strutz-Seebohm Nathalie , Decher Niels , Cui Jianmin , Schmitt Nicole , Düfer Martina , Wünsch Bernhard , Seebohm Guiscard 
Published: February 2021

AbstractLoss-of-function mutations in Kv7.1 often lead to long QT syndrome (LQTS), a cardiac repolarization disorder associated with increased risk of arrhythmia and subsequent sudden cardiac death. The discovery of agonisticIKsmodulators may offer a new potential strategy in pharmacological treatment of this disorder. The benzodiazepine (R)-L3 potently activates Kv7.1 channels and shortens action potential duration, thus may represent a starting point for drug development. However, the molecular mechanisms underlying modulation by (R)-L3 are still unknown. By combining alanine scanning mutagenesis, non-canonical amino acid incorporation, voltage-clamp electrophysiology and fluorometry, andin silicoprotein modelling, we showed that (R)-L3 not only stimulates currents by allosteric modulation of the pore domain but also alters the kinetics independently from the pore domain effects. We identified novel (R)-L3-interacting key residues in the lower S4-segment of Kv7.1 and observed an uncoupling of the outer S4 segment with the inner S5, S6 and selectivity filter segments. Summarizing, we provide structural and functional evidence for two independent Kv7.1 activating mechanisms by a single modulator.
A variational method for calculating the longitudinal deformation of a shield tunnel in soft soil caused by grouting under tunnel
Authors: Di Honggui , Huang Shihao , Fu Longlong , Wang Binglong 
Published: February 2021

Purpose
The paper aims to predict longitudinal deformation of a tunnel caused by grouting under the tunnel bottom in advance according to the grouting parameters, which can ensure the safety of the tunnel structure during the grouting process and also help to design the grouting parameters.

Design/methodology/approach
The paper adopted the analytical approach for calculating the longitudinal deformation of a shield tunnel caused by grouting under a tunnel, including usage of the Mindlin’s solution, the minimum potential energy principle and case validation.

Findings
The paper provides a variational method for calculating the longitudinal deformation of a shield tunnel in soft soil caused by grouting under the tunnel, which has high computational efficiency and accuracy.

Originality/value
This paper fulfils an identified need to study how the longitudinal deformation of a shield tunnel in soft soil caused by grouting under the tunnel can be calculated.
Green innovation: a multidomain systematic review
Authors: Oduro Stephen , Maccario Guglielmo , De Nisco Alessandro 
Published: February 2021

PurposeThis paper examines the status and evolution of green innovation research from 1948 to 2018.Design/methodology/approachUsing a systematic review of 293 peer-reviewed scholarly articles, the authors classify journal outlets, publication trends, research methods (research type, approach, design), themes/topics focus, country and regional distribution and theoretical perspectives, identifying main trends. They apply mixed methodologies, integrating both content and descriptive analyses.FindingsResults reveal the following critical conclusions: (1) publication trends disclose a steady growth of interest in green innovation research in the last decade (2011–2018), with most of the articles appearing in top-ranked journal outlets; (2) empirical studies involving quantitative surveys dominate the field over other methods like experiments, case studies (qualitative) and conceptual models; (3) research themes/topics are multi-perspectives, covering management and strategic dimension of green innovation (e.g. green innovation integration and adoption strategy; collaboration and networking in green innovation; green innovation management systems, green supply chain management, etc.), performance (financial, non-financial and both), drivers/antecedents and consumer green behavior; however, the “management and strategy” papers are by far higher; (4) studies are preponderately multi-country focused, concentrated in Europe and Australasia, with a low concentration in emerging markets like Africa and South America; And (5) the field lacks the adoption and development of novel theories. So far, the research fields principally focus on the “Porter hypothesis” and resource-based view in terms of the theory-driven studies. Based on these findings, knowledge gaps are identified, as are limitations and actionable agenda for future research.Originality/valueAs the first systematic review to adopt a comprehensive, holistic approach in synthesizing and summarizing research vis-à-vis the phenomenon of green innovation, the study offers practitioners and researchers an insightful understanding of the relevant issues that have been investigated on green innovation, thereby anchoring the evolutions for further sustainable-oriented research and improvement in management practices.
Learning style instruments in Arab countries: an analysis of existing literature
Authors: Yousef Darwish Abdulrahman 
Published: February 2021

Purpose
The purpose of this study is to examine learning style instruments used in Arab countries to measure higher education students’ learning styles, identify the most common instruments and determine whether the reliability and validity of these instruments have been verified in Arab contexts.

Design/methodology/approach
A comprehensive review of the existing literature using several databases and search engines. Descriptive statistics, such as frequencies and percentages were used to present the results.

Findings
There are only a few published studies related to learning styles in Arab countries, with the majority published between 2012 and 2016 using samples drawn from Saudi Arabia, the United Arab Emirates and Iraq. The most common learning style instrument is the Felder–Silverman/Solomon Index of Learning Styles. The reliability and validity of this instrument require further investigation.

Research limitations/implications
This study is not without limitations. First, it covers only publications in the English language. Second, the paper focuses on research involving higher education students. Third, only research that was available online was used in this study. Nonetheless, the findings have several implications for researchers, educators and human resource development managers. For researchers, this study highlights research gaps that need to be filled. It also serves as a basis for more analytical and in-depth studies. The data also helps educators become more informed about the learning style instruments commonly used in the Arab context and whether the results from these instruments are dependable. Human resource development managers can draw on these findings to choose instruments that have proven reliable and valid.

Originality/value
This study is the first attempt to examine learning style instruments used in Arab countries and to explore whether the reliability and validity of these instruments have been verified in Arab contexts. This paper is a useful contribution to research into learning styles and learning style instruments.
Weighted grey relational analysis to evaluate multilevel dispatching rules in wafer fabrication
Authors: Chia Yee Goh , Jeng Feng Chin , Chik Mohd Azizi Bin , Mokhtar Mohzani 
Published: February 2021

PurposeThis research proposes weighted grey relational analysis (WGRA) method to evaluate the performance of 325 multilevel dispatching rules in the wafer fabrication process.Design/methodology/approachThe research methodology involves multilevel dispatching rule generation, simulations, WGRA and result analysis. A complete permutation of multilevel dispatching rules, including the partial orders, is generated from five basic rules. Performance measures include cycle time, move, tool idling and queue time. The simulation model and data are obtained from a wafer fab in Malaysia. Two seasons varying in customer orders and objective weights are defined. Finally, to benchmark performance and investigate the effect of varying values of coefficient, the models are compared against TOPSIS and VIKOR.FindingsResults show that the seasons prefer different multilevel dispatching rules. In Normal season, the ideal first basic dispatching rule is critical ratio (CR) and CR followed by shortest processing time (SPT) is the best precedence pairing. In Peak season, the superiority of the rule no longer heavily relies on the first basic rule but rather depends on the combination of tiebreaker rules and on-time delivery (OTD) followed by CR is considered the best precedence pairing. Compared to VIKOR and TOPSIS, WGRA generates more stable rankings in this study. The performance of multicriteria decision-making (MCDM) methods is influenced by the data variability, as a higher variability produces a much consistent ranking.Research limitations/implicationsAs research implications, the application illustrates the effectiveness and practicality of the WGRA model in analyzing multilevel dispatching rules, considering the complexity of the semiconductor wafer fabrication system. The methodology is useful for researchers wishing to integrate MCDM model into multilevel dispatching rules. The limitation of the research is that the results were obtained from a simulation model. Also, the rules, criteria and weights assigned in WGRA were decided by the management. Lastly, the distinguishing coefficient is fixed at 0.5 and the effect to the ranking requires further study.Originality/valueThe research is the first deployment WGRA in ranking multilevel dispatching rules. Multilevel dispatching rules are rarely studied in scheduling research although studies show that the tiebreakers affect the performances of the dispatching rules. The scheduling reflects the characteristics of wafer fabrication and general job shop, such as threshold and look-ahead policies.