bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rats spontaneously perceive global motion direction of drifting plaids
Authors: Matteucci Giulio , Zattera Benedetta , Marotti Rosilari Bellacosa , Zoccolan Davide 
Published: February 2021

AbstractComputing global motion direction of extended visual objects is a hallmark of primate high-level vision. Although neurons selective for global motion have also been found in mouse visual cortex, it remains unknown whether rodents can combine multiple motion signals into global, integrated percepts. To address this question, we trained two groups of rats to discriminate either gratings (G group) or plaids (i.e., superpositions of gratings with different orientations; P group) drifting horizontally along opposite directions. After the animals learned the task, we applied a visual priming paradigm, where presentation of the target stimulus was preceded by the brief presentation of either a grating or a plaid. The extent to which rat responses to the targets were biased by such prime stimuli provided a measure of the spontaneous, perceived similarity between primes and targets. We found that gratings and plaids, when uses as primes, were equally effective at biasing the perception of plaid direction for the rats of the P group. Conversely, for G group, only the gratings acted as effective prime stimuli, while the plaids failed to alter the perception of grating direction. To interpret these observations, we simulated a decision neuron reading out the representations of gratings and plaids, as conveyed by populations of either component or pattern cells (i.e., local or global motion detectors). We concluded that the findings for the P group are highly consistent with the existence of a population of pattern cells, playing a functional role similar to that demonstrated in primates. We also explored different scenarios that could explain the failure of the plaid stimuli to elicit a sizable priming magnitude for the G group. These simulations yielded testable predictions about the properties of motion representations in rodent visual cortex at the single-cell and circuitry level, thus paving the way to future neurophysiology experiments.
Reconstitution of ultrawide DNA origami pores in liposomes for transmembrane transport of macromolecules
Authors: Fragasso Alessio , Franceschi Nicola De , Stömmer Pierre , van der Sluis Eli O. , Dietz Hendrik , Dekker Cees 
Published: February 2021

AbstractMolecular traffic across lipid membranes is a vital process in cell biology that involves specialized biological pores with a great variety of pore diameters, from fractions of a nanometer to >30 nm. Creating artificial membrane pores covering similar size and complexity will aid the understanding of transmembrane molecular transport in cells, while artificial pores are also a necessary ingredient for synthetic cells. Here, we report the construction of DNA origami nanopores that have an inner diameter as large as 30 nm. We developed new methods to successfully insert these ultrawide pores into the lipid membrane of giant unilamellar vesicles (GUVs) by administering the pores concomitantly with vesicle formation in an inverted-emulsion cDICE technique. The reconstituted pores permit the transmembrane diffusion of large macromolecules such as folded proteins, which demonstrates the formation of large membrane-spanning open pores. The pores are size selective as dextran molecules with a diameter up to 22 nm can traverse the pores, whereas larger dextran molecules are blocked. By FRAP measurements and modelling of the GFP influx rate, we find that up to hundreds of pores can be functionally reconstituted into a single GUV. Our technique bears great potential for applications across different fields from biomimetics, synthetic biology, to drug delivery.
Cyclophilin A regulates protein phase separation and mitigates haematopoietic stem cell aging
Authors: Maneix Laure , Iakova Polina , Moree Shannon E. , King Jordon C.K. , Sykes David B. , Hill Cedric T. , Saez Borja , Spooner Eric , Krause Daniela S. , Sahin Ergun , Berk Bradford C. , Scadden David T. , Catic André 
Published: February 2021

AbstractLoss of protein quality is a driving force of aging1. The accumulation of misfolded proteins represents a vulnerability for long-lived cells, such as haematopoietic stem cells. How these cells, which have the ability to reconstitute all haematopoietic lineages throughout life2, maintain their regenerative potential and avert the effects of aging is poorly understood. Here, we determined the protein content in haematopoietic stem and progenitor cells to identify prevalent chaperones that support proteome integrity. We identified Peptidyl-Prolyl Isomerase A (PPIA or Cyclophilin A) as the dominant cytosolic foldase in this cell population. Loss of PPIA accelerated aging in the mouse stem cell compartment. In an effort to define targets of PPIA, we found that RNA- and DNA-binding proteins are common substrates of this chaperone. These proteins are enriched in intrinsically disordered regions (IDRs), which can catalyse protein condensation3. Isomerized target prolines are almost exclusively located within IDRs. We discovered that over 20% of PPIA client proteins are known to participate in liquid-liquid phase separation, enabling the formation of supramolecular membrane-less organelles. Using the poly-A binding protein PABPC1 as an example, we demonstrate that PPIA promotes phase separation of ribonucleoprotein particles, thereby increasing cellular stress resistance. Haematopoietic stem cell aging is associated with a decreased expression of PPIA and reduced synthesis of intrinsically disordered proteins. Our findings link the ubiquitously expressed chaperone PPIA to phase transition and identify macromolecular condensation as a potential determinant of the aging process in haematopoietic stem cells.
Automatic recognition of macaque facial expressions for detection of affective states
Authors: Morozov Anna , Parr Lisa , Gothard Katalin , Paz Rony , Pryluk Raviv 
Published: February 2021

AbstractInternal affective states produce external manifestations such as facial expressions. In humans, the Facial Action Coding System (FACS) is widely used to objectively quantify the elemental facial action-units (AUs) that build complex facial expressions. A similar system has been developed for macaque monkeys - the Macaque Facial Action Coding System (MaqFACS); yet unlike the human counterpart, which is already partially replaced by automatic algorithms, this system still requires labor-intensive coding. Here, we developed and implemented the first prototype for automatic MaqFACS coding. We applied the approach to the analysis of behavioral and neural data recorded from freely interacting macaque monkeys. The method achieved high performance in recognition of six dominant AUs, generalizing between conspecific individuals (Macaca mulatta) and even between species (Macaca fascicularis). The study lays the foundation for fully automated detection of facial expressions in animals, which is crucial for investigating the neural substrates of social and affective states.
Elementary growth modes/vectors and minimal autocatalytic sets for kinetic/constraint-based models of cellular growth
Authors: Müller Stefan 
Published: February 2021

AbstractElementary vectors are fundamental objects in polyhedral geometry. In metabolic pathway analysis, elementary vectors range from elementary flux modes (of the flux cone) and elementary flux vectors (of a flux polyhedron) via elementary conversion modes (of the conversion cone) to minimal cut sets (of a dual polyhedron) in computational strain design.To better understand cellular phenotypes with optimal (or suboptimal) growth rate, we introduce and analyze classes of elementary vectors for models of cellular growth.Growth modes(GMs) only depend on stoichiometry, but not on growth rate or concentrations; they are elements of the growth cone.Elementarygrowth modes (EGMs) are conformally nondecomposable GMs; unlike elementary flux modes, they are not support-minimal, in general. Most importantly, every GM can be written as a conformal sum of EGMs.Growth vectors(GVs) andelementarygrowth vectors (EGVs) also depend on growth rate, concentrations, and linear constraints; they are elements of a growth polyhedron. Again, every GV can be written as a conformal sum of EGVs. To relate the new concepts to other branches of theory, we defineautocatalyticGMs and the corresponding(minimal) autocatalytic setsof reactions.As a case study, we consider whole cell models (simple kinetic models of self-fabrication). First, we use EGMs to derive an upper bound for growth rate that only depends on enzyme kinetics. Next, we study growth rate maximization (via control parameters for ribosome kinetics). In particular, we analyzegrowth states(GSs) andelementarygrowth states (EGSs) as introduced in [de Groot et al, 2020]. Unlike EGMs, EGSs depend on (metabolite) concentrations and growth rate. Most importantly, (i) we show that EGSs are support-minimal, (ii) we give a simple proof for the fact that maximum growth rate is attained at an EGS, and (iii) we show that, at every optimal EGS, the ribosome capacity constraint is active. Finally, we determine the dependence of EGSs on growth rate, and we study the relation between EGSs and minimal autocatalytic sets, EGMs, and elementary flux modes. Along the way, we point out (and resolve) mathematical issues in [de Groot et al, 2020].
Towards a systematic characterization of protein complex function: a natural language processing and machine-learning framework
Authors: Sharma Varun S. , Fossati Andrea , Ciuffa Rodolfo , Buljan Marija , Williams Evan G. , Chen Zhen , Shao Wenguang , Pedrioli Patrick G.A. , Purcell Anthony W. , Rodríguez Martínez María , Song Jiangning , Manica Matteo , Aebersold Ruedi , Li Chen 
Published: February 2021

SummaryIt is a general assumption of molecular biology that the ensemble of expressed molecules, their activities and interactions determine biological processes, cellular states and phenotypes. Quantitative abundance of transcripts, proteins and metabolites are now routinely measured with considerable depth via an array of “OMICS” technologies, and recently a number of methods have also been introduced for the parallel analysis of the abundance, subunit composition and cell state specific changes of protein complexes. In comparison to the measurement of the molecular entities in a cell, the determination of their function remains experimentally challenging and labor-intensive. This holds particularly true for determining the function of protein complexes, which constitute the core functional assemblies of the cell. Therefore, the tremendous progress in multi-layer molecular profiling has been slow to translate into increased functional understanding of biological processes, cellular states and phenotypes. In this study we describe PCfun, a computational framework for the systematic annotation of protein complex function using Gene Ontology (GO) terms. This work is built upon the use of word embedding— natural language text embedded into continuous vector space that preserves semantic relationships— generated from the machine reading of 1 million open access PubMed Central articles. PCfun leverages the embedding for rapid annotation of protein complex function by integrating two approaches: (1) an unsupervised approach that obtains the nearest neighbor (NN) GO term word vectors for a protein complex query vector, and (2) a supervised approach using Random Forest (RF) models trained specifically for recovering the GO terms of protein complex queries described in the CORUM protein complex database. PCfun consolidates both approaches by performing the statistical test for the enrichment of the top NN GO terms within the child terms of the predicted GO terms by RF models. Thus, PCfun amalgamates information learned from the gold-standard protein-complex database, CORUM, with the unbiased predictions obtained directly from the word embedding, thereby enabling PCfun to identify the potential functions of putative protein complexes. The documentation and examples of the PCfun package are available athttps://github.com/sharmavaruns/PCfun. We anticipate that PCfun will serve as a useful tool and novel paradigm for the large-scale characterization of protein complex function.
Modeling the SARS-CoV-2 nsp1–5’-UTR complex via extended ensemble simulations
Authors: Sakuraba Shun , Qilin Xie , Kasahara Kota , Iwakiri Junichi , Kono Hidetoshi 
Published: February 2021

AbstractNonstructural protein 1 (nsp1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a 180-residue protein that blocks translation of host mRNAs in SARS-CoV-2-infected cells. Although it is known that SARS-CoV-2’s own RNA evades nsp1’s host translation shutoff, the molecular mechanism underlying the evasion was poorly understood. We performed an extended ensemble molecular dynamics simulation to investigate the mechanism of the viral RNA evasion. Simulation results showed that the stem loop structure of the SARS-CoV-2 RNA 5’-untranslated region (SL1) is recognized by both nsp1’s globular region and intrinsically disordered region. The recognition presumably enables selective translation of viral RNAs. Cluster analysis of the binding mode and detailed analysis of the binding poses revealed several residues involved in the SL1 recognition mechanism. The simulation results imply that the nsp1 C-terminal helices are lifted from the 40Sribosome upon the binding of SL1 to nsp1, unblocking translation of the viral RNA.
Domestication effects on immune response: comparison of cell-mediated immune competence in wild and domesticated Bengalese finch
Authors: Suzuki Kenta , Okanoya Kazuo 
Published: February 2021

ABSTRACTDomesticated Bengalese finch (Lonchura striatavar.domestica)lack natural selection pressures and consequently have more complex songs and altered behavioural and psychological traits when compared to their wild ancestor, the white-rumpud munia (Lonchura striata). Clarifying the sexual traits and life history trade-offs in Bengal finches will be help to improve our understanding of the evolution of complex songs and domesticated traits. Here, we have assessed the immune competence of the Bengalese finch and the white-rumped munia using phytohemagglutinin (PHA) tests to create an index of cell-mediated immune responses. We found that the Bengalese finch had a significantly larger immunocompetence than the white-rumped munia, indicating that they devote more resources to both immunity and reproduction. Thus, there is no trade-off but a positive relationship between immunocompetence and reproductive traits, which may be related to the release from natural selection pressures. These results will be useful in understanding the mechanisms by which domestication-induced changes due to a lack of natural selection pressure affect behavioural and physiological changes.
Genetic and epigenetic determinants of reactivation of Mecp2 and the inactive X chromosome in neural stem cells
Authors: Mira-Bontenbal Hegias , Tan Beatrice , Gontan Cristina , Goossens Sander , Boers R.G. , Boers J. , Dupont Catherine , van Royen Martin , van IJcken Wilfred , French Pim , Bedalov Toni , Gribnau Joost 
Published: February 2021

AbstractRett Syndrome is a neurodevelopmental disorder in girls that is caused by heterozygous inactivation of the chromatin remodeler geneMECP2. Rett Syndrome may therefore be treated by reactivation of the wild type copy ofMECP2from the inactive X chromosome. Most studies that modelMecp2reactivation have used mouse fibroblasts rather than neural cells, which would be critical for phenotypic reversal, and rely on fluorescent reporters that lack adequate sensitivity. Here, we present a mouse model system for monitoring Mecp2 reactivation that is more sensitive and versatile than any bioluminescent and fluorescent system currently available. The model consists of neural stem cells derived from female mice with a dual reporter system where MECP2 is fused to NanoLuciferase and TdTomato on the inactive X chromosome. We show by bioluminescence and fluorescence thatMecp2is synergistically reactivated by 5-Aza treatment andXistknockdown. As expected, other genes on the inactive X chromosome are also reactivated, the majority of which overlaps with genes reactivated early during reprogramming of mouse embryonic fibroblasts to iPSCs. Genetic and epigenetic features such as CpG density, SINE elements, distance to escapees and CTCF binding are consistent indicators of reactivation, whereas different higher order chromatin areas are either particularly prone or resistant to reactivation. Our MeCP2 reactivation monitoring system thereby suggests that genetic and epigenetic features on the inactive X chromosome affect reactivation of its genes, irrespective of cell type or procedure of reactivation.
Bird strike virtual testing for preliminary airframe design
Authors: Perdikoulis Petros V. , Giannopoulos Ioannis K. , Theotokoglou Efstathios E. 
Published: February 2021

Purpose
The purpose of this paper is to use numerical methods early in the airframe design process and access the structural performance of wing leading edge devices made of different materials and design details, under bird strike events.

Design/methodology/approach
Explicit finite element analysis was used to numerically model bird strike events.

Findings
Structural performance charts related to materials and general design details were drawn to explore the design space dictated by the current applicable airworthiness requirements.

Practical implications
This paper makes use of the current capability in the numerical tools available for structural simulations and exposes the existing limitations in the terms of material modelling, material properties and fracture simulation using continuum damage mechanics. Such results will always be in the need of fine-tuning with experimental testing, yet the tools can shed some light very early in the design process in a relative inexpensive manner, especially for design details down selection like materials to use, structural thicknesses and even design arrangements.

Originality/value
Bird strike simulations have been successfully used on aircraft design, mainly at the manufactured articles design validation, testing and certification. This paper presents a hypothetical early design case study of leading edge devices for appropriate material and skin thickness down selection.
Mind the gap: the reality of remote learning during COVID-19
Authors: Osborne Sarah , Hogarth Kate 
Published: February 2021

Purpose
Students, faculty staff and universities thrive and reach their full potential through planning and a sense of community. In a few short weeks, COVID-19 unravelled months of planning, separated the university community and shifted tertiary education to remote learning. This created a triangulated expectations–performance gap as to what could be reasonably implemented to support student learning, support educators and provide a continued sense of community. The purpose of this paper is to consider how educators could implement strategies to close the expectations gap created by COVID-19 remote learning.

Design/methodology/approach
The authors consider the expectations gap through pre-COVID-19 pedagogical strategies and teaching methods, then outline how we modified them into COVID-19 teaching approaches and designs.

Findings
The authors found that although expectations differ between university administration, students and faculty staff, there are a number of paths educators can take to close the expectations gap, facilitate interaction and engagement while gently encouraging self-driven student learning in a difficult time.

Originality/value
The practical exemplars identify steps educators can take as support mechanisms for student learners to embrace and take control of their own education in the remote learning environment and convey the importance of maintaining a sense of belonging. This creates an improved teaching environment for educators and an enhanced learning environment for students.
Devil's Peak: The craft conundrum
Authors: Harrington Gareth , Samuelsson Mikael 
Published: February 2021

Subject area of the teaching case:
The case can be used in the subject area of strategy particularly with a focus on emerging markets.

Student level:
This case is aimed at use in MBA- or Masters-level courses, or executive education programmes in strategy, entrepreneurship or business modelling. It will also provide insights into small to medium enterprises operating in emerging markets.

Brief overview of the teaching case:
Devil's Peak is the largest craft beer brewer in South Africa. This case provides context to the craft beer market in South Africa, a highly fragmented and diverse yet dynamic market. The case further explores the business strategy behind Devil's Peak's success, the importance of strategic decisions, growth decisions, and product portfolio selections' impact on business strategy. Devil's Peak experienced rapid growth phases that have come with various trials and tribulations and the case explores the issues and decisions around rapid growth businesses.

Expected learning outcomes:

– To analyse a market before entering it using Porter's Five Forces or other tools.
– To assess, as well as understand, the complexities and issues arising from rapid growth in entrepreneurial operations.
– To evaluate different growth strategies — organic growth versus inorganic growth, like acquired growth.
– To make product portfolio selection decisions and the strategic importance of which products to invest in and grow, using tools like the Boston Consulting Group (BCG) growth-share matrix or other tools.