bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-Regulon: A novel “soft-curation” approach supported by a semantic enriched reading for RegulonDB literature
Authors: Lithgow-Serrano Oscar , Gama-Castro Socorro , Ishida-Gutiérrez Cecilia , Collado-Vides Julio 
Published: April 2020

AbstractManual curation is a bottleneck in the processing of the vast amounts of knowledge present in the scientific literature in order to make such knowledge available in computational resources e.g., structured databases. Furthermore, the extraction of content is by necessity limited to the pre-defined concepts, features and relationships that conform to the model inherent in any knowledgebase. These pre-defined elements contrast with the rich knowledge that natural language is capable of conveying. Here we present a novel experiment of what we call “soft curation” supported by an ad-hoc tuned robust natural language processing development that quantifies semantic similarity across all sentences of a given corpus of literature. This underlying machine supports novel ways to navigate and read within individual papers as well as across papers of a corpus. As a first proof-of-principle experiment, we applied this approach to more than 100 collections of papers, selected from RegulonDB, that support knowledge of the regulation transcription initiation inE. coli K-12, resulting in L-Regulon (L for “linguistic”) version 1.0. Furthermore, we have initiated the mapping of RegulonDB curated promoters, promoters, to their evidence sentence in the given publication. We believe this is the first step in a novel approach for users and curators, in order to increase the accessibility of knowledge in ways yet to be discovered.
Temporal codes of visual working memory in the human cerebral cortex
Authors: Noguchi Yasuki , Kakigi Ryusuke 
Published: April 2020

AbstractVisual working memory (vWM) is an important ability required for various cognitive tasks although its neural underpinnings remain controversial. While many studies have focused on theta (4-7 Hz) and gamma (> 30 Hz) rhythms as a substrate of vWM, here we show that temporal signals embedded in alpha (8-12 Hz) and beta (13-30 Hz) bands can be a good predictor of vWM capacity. Neural activity of healthy human participants was recorded with magnetoencephalography when they performed a classical vWM task (change detection). We analyzed changes in inter-peak intervals (IPIs) of oscillatory signals along with an increase in WM load (a number of to-be-memorized items, 1-6). Results showed a load-dependent reduction of IPIs in the parietal and frontal regions, indicating that alpha/beta rhythms became faster when multiple items were stored in vWM. Furthermore, this reduction in IPIs was positively correlated with individual vWM capacity, especially in the frontal cortex. Those results indicate that vWM is represented as a change in oscillation frequency in the human cerebral cortex.
Tinamou egg color displacement at ecoregion co-partitioning
Authors: Li Qin , Wang Silu 
Published: April 2020

AbstractThe divergence of reproductive traits frequently underpins the evolution of reproductive isolation. One of the most enduring puzzles on this subject concerns the variability in egg coloration among species of tinamou (Tinamidae), endemic to neotropics. Here we investigated the hypothesis that tinamou egg coloration is a mating signal and its diversification was driven by reinforcement. For most tinamou species, the male guards the nest that is sequentially visited and laid eggs in by multiple females. The colorations of the existing eggs in the nest could signal mate quality and species identities to the upcoming females, preventing costly hybridization, thus were selected to diverge among species (Mating Signal Character Displacement Hypothesis). If so, two predictions should follow: (1) egg colors should coevolve with known mating signals as the tinamou lineages diverged; (2) species that partition similar ecoregions should display different egg colors. The tinamou songs are important mating signals and are highly divergent among species. We found that the egg luminance was significantly associated with the first principal component of the song variables, which supports prediction (1). In addition, we found support for (2): tinamou species that co-partition ecoregions tend to display different egg colors, controlling for song variation. Egg color and songs could be multimodal mating signals that are divergently selected as different tinamou species diverged. Mating signal evolution could be opportunistic and even exploit post-mating trait as premating signals that undergo character displacement at sympatry.
Specific mutations in SARS-CoV2 RNA dependent RNA polymerase and helicase alter protein structure, dynamics and thus function: Effect on viral RNA replication
Authors: Begum Feroza , Mukherjee Debica , Das Sandeepan , Thagriki Dluya , Tripathi Prem Prakash , Banerjee Arup Kumar , Ray Upasana 
Published: April 2020

1.AbstractThe open reading frame (ORF) 1ab of SARS-CoV2 encodes non-structural proteins involved in viral RNA functions like translation and replication including nsp1-4; 3C like proteinase; nsp6-10; RNA dependent RNA polymerase (RdRp); helicase and 3’-5’ exonuclease. Sequence analyses of ORF1ab unravelled emergence of mutations especially in the viral RdRp and helicase at specific positions, both of which are important in mediating viral RNA replication. Since proteins are dynamic in nature and their functions are governed by the molecular motions, we performed normal mode analyses of the SARS-CoV2 wild type and mutant RdRp and helicases to understand the effect of mutations on their structure, conformation, dynamics and thus function. Structural analyses revealed that mutation of RdRp (at position 4715 in the context of the polyprotein/ at position 323 of RdRp) leads to rigidification of structure and that mutation in the helicase (at position 5828 of polyprotein/ position 504) leads to destabilization increasing the flexibility of the protein structure. Such structural modifications and protein dynamics alterations might alter unwinding of complex RNA stem loop structures, the affinity/ avidity of polymerase RNA interactions and in turn the viral RNA replication. The mutation analyses of proteins of the SARS-CoV2 RNA replication complex would help targeting RdRp better for therapeutic intervention.
Lsr2 is a nucleoid-associated protein that exerts pleiotropic effects on mycobacterial cellular processes
Authors: Kołodziej Marta , Trojanowski Damian , Bury Katarzyna , Hołówka Joanna , Paściak Mariola , Matysik Weronika , Kąkolewska Hanna , Feddersen Helge , Giacomelli Giacomo , Bramkamp Marc , Konieczny Igor , Zakrzewska-Czerwińska Jolanta 
Published: April 2020

AbstractLsr2 is involved in maintaining chromosome structure in asymmetrically dividing mycobacteria and is essential in the tubercle bacillus (M. tuberculosis) during infection. Here, we report that a lack of Lsr2 profoundly impacts the mycobacterial cell morphology and the properties of the cell envelope resulting in the formation of smooth, short and antibiotics sensitive cells. Lsr2 forms large and dynamic nucleoprotein complexesin vivoand deletion oflsr2gene exerts a profound effect on the replication time and replisome dynamics. We suggest that the Lsr2 nucleoprotein complexes may contribute to maintaining the proper organization of the newly synthesized DNA. Moreover, we demonstrate that the N-terminal oligomerization domain of Lsr2 is indispensable for the formation of nucleoprotein complexesin vivo. Collectively, our results indicate that Lsr2 exerts a pleiotropic effect on cellular processes and appears to be an attractive target for the development of a novel antitubercular drugs.
High-throughput organoid screening enables engineering of intestinal epithelial composition
Authors: Mead Benjamin E. , Hattori Kazuki , Levy Lauren , Vukovic Marko , Sze Daphne , Matute Juan D. , Duan Jinzhi , Langer Robert , Blumberg Richard S. , Ordovas-Montanes Jose , Shalek Alex K. , Karp Jeffrey M. 
Published: April 2020

SummaryBarrier tissue epithelia play an essential role in maintaining organismal homeostasis, and changes in their cellular composition have been observed in multiple human diseases. Within the small intestinal epithelium, adult stem cells integrate diverse signals to regulate regeneration and differentiation, thereby establishing overall cellularity. Accordingly, directing stem cell differentiation could provide a tractable approach to alter the abundance or quality of specialized cells of the small intestinal epithelium, including the secretory Paneth, goblet, and enteroendocrine populations. Yet, to date, there has been a lack of suitable tools and rigorous approaches to identify biological targets and pharmacological agents that can modify epithelial composition to enable causal testing of disease-associated changes with novel therapeutic candidates. To empower the search for epithelia-modifying agents, we establish a first-of-its-kind high-throughput phenotypic organoid screen. We demonstrate the ability to screen thousands of samples and uncover biological targets and associated small molecule inhibitors which translate toin vivo. This approach is enabled by employing a functional, cell-type specific, scalable assay on an organoid model designed to represent the physiological cues ofin vivoPaneth cell differentiation from adult intestinal stem cells. Further, we miniaturize and adapt the organoid culture system to enable automated plating and screening, thereby providing the ability to test thousands of samples. Strikingly, in our screen we identify inhibitors of the nuclear exporter Xpo1 modulate stem cell fate commitment by inducing a pan-epithelial stress response combined with an interruption of mitogen signaling in cycling intestinal progenitors, thereby significantly increasing the abundance of Paneth cells independent of known WNT and Notch differentiation cues. We extend our observationin vivo, demonstrating that oral administration of Xpo1 inhibitor KPT-330 at doses 1,000-fold lower than conventionally used in hematologic malignancies increases Paneth cell abundance. In total, we provide a framework to identify novel biological cues and therapeutic leads to rebalance intestinal stem cell differentiation and modulate epithelial tissue composition via high-throughput phenotypic screening in rationally-designed organoid model of differentiation.
Promoter Choice: Who Should Drive the CAR in T Cells?
Authors: Rad SM Ali Hosseini , Poudel Aarati , Yi Tan Grace Min , McLellan Alexander D. 
Published: April 2020

AbstractChimeric antigen receptor (CAR) T cell therapy is an effective treatment for B cell malignancies, with emerging potential for the treatment of other hematologic cancers and solid tumors. The strength of the promoter within the CAR cassette will alter CAR-polypeptide levels on the cell surface of the T cell – impacting on the kinetics of activation, survival and memory cell formation in T cells. In addition to the CAR, promoters can be used to drive other genes of interest to enhance CAR T cell function. Expressing multiple genes from a single RNA transcript can be effectively achieved by linking the genes via a ribosomal skip site. However, promoters may differ in their ability to transcribe longer RNAs, or could interfere with lentiviral production, or transduction frequencies. In this study we compared the ability of the strong well-characterized promoters CMV, EF-1, hPGK and RPBSA to drive functional expression of a single RNA encoding three products: GFP, CAR, plus an additional cell-survival gene, Mcl-1. Although the four promoters produced similarly high lentiviral titres, EF-1 gave the best transduction efficacy of primary T cells. Major differences were found in the ability of the promoters to drive expression of long RNA encoding GFP, CAR and Mcl-1, highlighting promoter choice as an important consideration for gene therapy applications requiring the expression of long and complex mRNA.
An automated homecage system for multiwhisker detection and discrimination learning in mice
Authors: Bernhard Sarah M. , Lee Jiseok , Zhu Mo , Hsu Alex , Erskine Andrew , Hires Samuel A. , Barth Alison L. 
Published: April 2020

AbstractAutomated, homecage behavioral training for rodents has many advantages: it is low stress, requires little interaction with the experimenter, and can be easily manipulated to adapt to different experimental condition. We have developed an inexpensive, Arduino-based, homecage training apparatus for sensory association training in freely-moving mice using multiwhisker air current stimulation coupled to a water reward. Animals learn this task readily, within 1-2 days of training, and performance progressively improves with training. We examined the parameters that regulate task acquisition using different stimulus intensities, directions, and reward valence. Learning was assessed by comparing anticipatory licking for the stimulus compared to the no-stimulus (blank) trials. At high stimulus intensities (>9 psi), animals showed markedly less participation in the task. Conversely, very weak air current intensities (1-2 psi) were not sufficient to generate rapid learning behavior. At intermediate stimulus intensities (5-6 psi), a majority of mice learned that the multiwhisker stimulus predicted the water reward after 24-48 hrs of training. Both exposure to isoflurane and lack of whiskers decreased animals’ ability to learn the task. Perceptual learning was assessed and following training at an intermediate stimulus intensity, perception was likely heightened as mice were able to transfer learning behavior when exposed to the lower stimulus intensity. Mice learned to discriminate between two directions of stimulation rapidly and accurately, even when the angular distance between the stimuli was <15 degrees. Switching the reward to a more desirable reward, aspartame, had little effect on learning trajectory. Our results show that a tactile association task in an automated homecage environment can be monitored by anticipatory licking to reveal rapid and progressive behavioral change. These Arduino-based, automated mouse cages enable high-throughput training that facilitate analysis of large numbers of genetically modified mice with targeted manipulations of neural activity.
Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell lung cancer cells
Authors: Park Kyeong-Yong , Kim Jiyeon 
Published: April 2020

AbstractIn human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhibited the TGF-β1-activated EMT through suppression of Wnt signaling, Smad and non-Smad signaling pathways. In addition, the cRGDfK also inhibited the expression of TGFβ1-induced mesenchymal marker genes and proteins. The anti-EMT effect of sunitinib was enhanced when cRGDfK was treated together. When sunitinib was treated with cRGDfK, the mRNA and protein expression levels of mesenchymal markers were decreased compared to the treatment with sunitinib alone. Co-treatment of cRGDfK has shown the potential to improve the efficacy of anticancer agents in combination with therapeutic agents that may be toxic at high concentrations. These results provide new and improved therapies for treating and preventing EMT-related disorders, such as lung fibrosis and cancer metastasis, and relapse.
Interleukin-17 pathway activation inEquus caballussupporting limb laminitis
Authors: Cassimeris Lynne , Engiles Julie B. , Galantino-Homer Hannah 
Published: April 2020

AbstractSupporting Limb Laminitis (SLL) is a painful and crippling secondary complication of orthopedic injuries and infections in horses, often resulting in euthanasia. Due to altered weight bearing, SLL causes structural alternations and inflammation of the interdigitating layers of specialized epidermal and dermal tissues, the lamellae, which suspend the equine distal phalanx from the hoof capsule. Activation of the interleukin-17 (IL-17)-dependent inflammatory pathway is an epidermal stress response that contributes to physiologic cutaneous wound healing as well as pathological skin conditions. To test the hypothesis that IL-17 pathway activation is involved in equine epidermal lamellae in SLL, we analyzed the expression of the IL-17 receptor subunit A and 11 genes upregulated by IL-17 in lamellar tissue isolated from Thoroughbreds euthanized due to naturally occurring SLL and in age and breed matched non-laminitic controls. The IL-17 Receptor A subunit was expressed in both non-laminitic and laminitic tissues. In severe acute SLL (n=7) compared to non-laminitic controls (n=8), quantitative PCR demonstrated ∼20-100 fold upregulation of ß defensin 4 (E. caballusgeneDEFB4B) andS100A9genes.DEFB4Bwas also upregulated in developmental (n=8), moderate acute (n=7), and severe chronic (n=5) samples. By RT-PCR,S100A8, MMP9, andPTSG2(COX2) expression was upregulated in most or all severe acute SLL samples, whereas several other genes,CCL2, CxCL8, TNFα, IL6andMMP1were detected in some, but not all, severe acute samples.PTGS2, CCL2, TNFαandIL6were also expressed in some, but not all, developmental and moderate acute disease stages. Moreover, expression ofDEFB4by in situ hybridization and calprotectin (S100A9/S100A8) protein by immunofluorescence was detected in keratinocytes, primarily in suprabasal cell layers, from SLL samples. These data support the hypothesis that the IL-17 inflammatory pathway is active in equine SLL, and that similarities exist between equine and human epidermal tissue responses to stresses and/or damage.
Remodeling of Chemotaxis is a Cornerstone of Bacterial Swarming
Authors: Partridge Jonathan D. , Nguyen Nhu Q. , Dufour Yann S. , Harshey Rasika M. 
Published: April 2020

AbstractMany bacteria use flagella-driven motility to swarm or move collectively over a surface terrain. Bacterial adaptations for swarming can include cell elongation, hyper-flagellation, recruitment of special stator proteins and surfactant secretion, among others. We recently demonstrated another swarming adaptation inEscherichia coli, wherein the chemotaxis pathway is remodeled to increase run durations (decrease tumble bias), with running speeds increased as well. We show here that the modification of motility parameters during swarming is not unique toE. coli, but shared by a diverse group of bacteria we examined –Proteus mirabilis, Serratia marcescens, Salmonella enterica, Bacillus subtilis, andPseudomonas aeruginosa– suggesting that altering the chemosensory physiology is a cornerstone of swarming.ImportanceBacteria within a swarm move characteristically in packs, displaying an intricate swirling motion where hundreds of dynamic packs continuously form and dissociate as the swarm colonizes increasing expanse of territory. The demonstrated property ofE. colito reduce its tumble bias and hence increase its run duration during swarming is expected to maintain/promote side-by-side alignment and cohesion within the bacterial packs. Here we observe a similar low tumble bias in five different bacterial species, both Gram positive and Gram negative, each inhabiting a unique habitat and posing unique problems to our health. The unanimous display of an altered run-tumble bias in swarms of all species examined here suggests that this behavioral adaptation is crucial for swarming.
Fostering creativity through online creative collaborative group projects
Authors: Raymundo Maria Rowena D.R. 
Published: April 2020

PurposeHigher education institutions (HEIs) frequently overlook the importance of encouraging creative thinking in students. A review of the prevailing practices in a fully online tertiary distance education (DE) institution revealed a lack of learning activities that foster creativity. The study aims to find out whether the creative collaborative group project is a feasible, effective and acceptable learning activity for fostering creativity in students of a fully online graduate-level DE course.Design/methodology/approachSeven groups of five to six graduate students each had five weeks to conceptualize, prepare and deliver a creative collaborative group project on lifelong learning using key concepts learned from the course.FindingsAll groups submitted well-crafted creative projects within the given time frame. Reflections on their experience positively correlated with known outcomes associated with creative skills. Students valued the experience and had a better understanding of the concepts. These support the feasibility, effectiveness and acceptability of the project for fostering creativity in a fully online DE institution.Research limitations/implicationsThe feasibility, effectiveness and acceptability may vary in different contexts; future iterations in the same and/or other courses are recommended.Practical implicationsThe creative collaborative group project is a feasible, effective and acceptable strategy for fostering creativity in online distance education.Social implicationsCreativity can be enhanced through appropriate online collaborative learning activities.Originality/valueThe study adds to the body of literature on the use of creative collaborative group projects to foster creativity in HEIs.
Investigating the managerial ‘‘nuts and bolts’’ for the construction industry
Authors: Yap Jeffrey Boon Hui , Chow Ian Ni 
Published: April 2020

PurposeManagerial shortfalls can considerably undermine the delivery performance of construction projects. This paper appraises the project management essentials (PMEs) for successful construction project delivery.Design/methodology/approachFollowing a detailed literature review, a questionnaire survey was developed encompassing 20 PMEs that were identified. An opinion questionnaire survey was used to facilitate data collection from key construction stakeholders in the Malaysian construction industry. The survey data were subjected to descriptive statistics and exploratory factor analysis.FindingsFindings indicated that the leading PMEs are competency of the project team, competency of project manager, good leadership, effective planning and control and realistic cost and time estimate. Spearman’s rank correlation tests affirmed a good agreement on the ranking of PMEs across stakeholder groups. The present study found that PMEs for construction have a total of four dimensions, namely: scope, communication and competence management; stakeholder commitment and collaborative engagement; construction time–cost planning and control; and environment, health, safety and quality management.Practical implicationsThe findings could potentially contribute to the development of appropriate project management best practices to address managerial shortfalls in Malaysia and other developing countries.Originality/valueThis paper bridges the identified knowledge gap about critical managerial dimensions for successful project management in construction. The present study adds to the existing body of knowledge around this under-explored area in the construction management literature.