bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atomic reconstruction of biomolecular structures from AFM images and quantitative validation of experimental data using simulated AFM scanning
Authors: Amyot Romain , Marchesi Arin , Franz Clemens M , Casuso Ignacio , Flechsig Holger 
Published: June 2021

AbstractWe provide the BioAFMviewer-Toolbox, an extension of our previously developed software platform for simulated AFM scanning of biomolecular structures and dynamics. The focus was on developing a toolbox of methods which employ simulated AFM scanning combined with quantitative analysis to facilitate the interpretation of resolution-limited AFM images. The key advancement is the automatized fitting of biomolecular structures to experimental AFM images, which allows to reconstruct 3D atomistic structures from AFM surface scans. Moreover, several methods for detailed analysis and comparison of surface topographies in simulated and experimental AFM images are provided. We demonstrate the applicability of the developed tools in the interpretation of high-speed AFM observations of proteins. The toolbox is implemented into the versatile interactive interface of the BioAFMviewer, which is a free software package available at www.bioafmviewer.com.
Disrupted choline clearance and sustained acetylcholine release in vivo by a common choline transporter coding variant associated with poor attentional control in humans
Authors: Donovan Eryn , Avila Cassandra , Klausner Sarah , Parikh Vinay , Fenollar-Ferrer Cristina , Blakely Randy D. , Sarter Martin 
Published: June 2021

AbstractTransport of choline via the neuronal high-affinity choline transporter (CHT; SLC5A7) is essential for cholinergic terminals to synthesize and release acetylcholine (ACh). In humans, we previously demonstrated an association between a common CHT coding substitution (rs1013940; Ile89Val) and reduced attentional control as well as attenuated frontal cortex activation. Here, we used a CRISPR/Cas9 approach to generate mice expressing the I89V substitution and assessed, in vivo, CHT-mediated choline transport, and ACh release. Relative to wild type (WT) mice, CHT-mediated clearance of choline in mice expressing one or two Val89 alleles was reduced by over 80% cortex and by over 50% in striatum. Choline clearance in CHT Val89 mice was further reduced by neuronal inactivation. Deficits in ACh release, 5 and 10 min after repeated depolarization at a low, behaviorally relevant frequency, support an attenuated reloading capacity of cholinergic neurons in mutant mice. The density of CHTs in total synaptosomal lysates and neuronal plasma-membrane-enriched fractions was not impacted by the Val89 variant, indicating a selective impact on CHT function. When challenged with a visual disruptor to reveal attentional control mechanisms, Val89 mice failed to adopt a more conservative response bias. Structural modeling revealed that Val89 may attenuate choline transport by altering conformational changes of CHT that support normal transport rates. Our findings support the view that diminished, sustained cholinergic signaling capacity underlies perturbed attentional performance in individuals expressing CHT Val89. The CHT Val89 mouse serves as a valuable model to study heritable risk for cognitive disorders arising from cholinergic dysfunction.Significance StatementAcetylcholine (ACh) signaling depends on the functional capacity of the neuronal choline transporter (CHT). Previous research demonstrated that humans expressing the common CHT coding variant Val89 exhibit attentional vulnerabilities and attenuated fronto-cortical activation during attention. Here, we find that mice engineered to express the Val89 variant exhibit reduced CHT-mediated choline clearance and a diminished capacity to sustain ACh release. Additionally, Val89 mice lack cognitive flexibility in response to an attentional challenge. These findings provide a mechanistic and cognitive framework for interpreting the attentional phenotype associated with the human Val89 variant and establish a model that permits a more invasive interrogation of CNS effects as well as the development of therapeutic strategies for those, including Val89 carriers, with presynaptic cholinergic perturbations.
Aerobiology in High Latitudes: Evidence of Bacteria Acting as Tracer of Warm Air Mass Advection reaching Northern Antarctic Peninsula
Authors: Cataldo Marcio , Evangelista Heitor , Pereira José Augusto Adler , Bertho Álvaro Luiz , Pellizari Vivian , Kuhn Emanuele , Sampaio Marcelo , da Cunha Kenya Dias , dos Santos Alencar Alexandre , Amaral Cesar 
Published: June 2021

ABSTRACTDespite the extent use of geochemical tracers to track warm air mass origin reaching the Antarctic continent, we present here evidences that microorganisms being transported by the atmosphere and deposited in fresh snow layers of Antarctic ice sheets do act as tracers of air mass advection from the Southern Patagonia region to Northern Antarctic Peninsula. We combined atmospheric circulation data with microorganism content in snow/firn samples collected in two sites of the Antarctic Peninsula (King George Island/Wanda glacier and Detroit Plateau) by using flow cytometer quantification. In addition, we cultivated, isolated and submitted samples to molecular sequencing to precise species classification. Viable gram-positive bacteria were found and recovered in different snow/firn layers samples, among dead and living cells, their number concentration was compared to northern wind component, stable isotopes of oxygen, δ18O, and the concentration of crustal elements (Fe, Ti and Ca). Use of satellite images combined with air mass back-trajectory analysis obtained from the NOAA/ HYSPLIT model corroborated the results.
Carbohydrate sulfation as a mechanism for fine-tuning Siglec ligands
Authors: Jung Jaesoo , Enterina Jhon R. , Bui Duong T. , Mozaneh Fahima , Lin Po-Han , Nitin  , Kuo Chu-Wei , Rodrigues Emily , Bhattacherjee Abhishek , Raeisimakiani Parisa , Daskhan Gour C. , St. Laurent Chris D. , Khoo Kay-Hooi , Mahal Lara K. , Zandberg Wesley F. , Huang Xuefei , Klassen John S. , Macauley Matthew S. 
Published: June 2021

AbstractThe immunomodulatory family of Siglecs recognize sialic acid-containing glycans as ‘self’, which is exploited in cancer for immune-evasion. The biochemical nature of Siglec ligands remains incompletely understood with emerging evidence suggesting the importance of carbohydrate sulfation. Here, we investigate how specific sulfate modifications affect Siglec ligands by overexpressing eight carbohydrate sulfotransferases (CHSTs) in five cell lines. Overexpression of three CHSTs (CHST1, CHST2, or CHST4) significantly enhances the binding of numerous Siglecs. Unexpectedly, two other CHSTs (Gal3ST2 and Gal3ST3) diminish Siglec binding, suggesting a new mode to modulate Siglec ligands via sulfation. Results are cell type dependent, indicating that the context in which sulfated glycans are presented is important. Moreover, pharmacological blockade of N- and O-glycan maturation reveals a cell type-specific pattern of importance for either class of glycan. Production of a highly homogenous CD33 (Siglec-3) fragment enabled a mass spectrometry-based binding assay to determine 10-fold and 3-fold enhanced affinity for Neu5Acα2-3(6-O-sulfo)Galβ1-4GlcNAc and Neu5Acα2-3Galβ1-4(6-O- sulfo)GlcNAc, respectively, over Neu5Acα2-3Galβ1-4GlcNAc. CD33 showed significant additivity in affinity (36-fold) for the disulfated ligand, Neu5Acα2-3(6-O-sulfo)Galβ1-4(6-O-sulfo)GlcNAc. Moreover, overexpression of both CHST1 and CHST2 in cells greatly enhanced the binding of several Siglecs, including CD33. Finally, we reveal that CHST1 is upregulated in numerous cancers, correlating with poorer survival rates and sodium chlorate sensitivity for the binding of Siglecs to cancer cell lines. These results provide new insights into carbohydrate sulfation as a modification that is a general mechanism for tuning Siglec ligands on cells, including in cancer.
Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system
Authors: Kubasova Nadiya , Alves-Pereira Clara F. , Gupta Saumya , Vinogradova Svetlana , Gimelbrant Alexander , Barreto Vasco M. 
Published: June 2021

ABSTRACTThe persistence of patterns of monoallelic expression is a controversial matter. We report a genome-wide in vivo transcriptomics approach based on allelic expression imbalance to evaluate whether the transcriptional allelic patterns of single murine hematopoietic stem cells (HSC) are still present in the respective differentiated clonal B-cell populations. For 14 genes, we show conclusive evidence for a remarkable persistence in HSC-derived B clonal cells of allele-specific autosomal transcriptional states already present in HSCs. In a striking contrast to the frequency of genes with clonal allelic expression differences in clones expanded without differentiation (up to 10%), we find that clones that have undergone multiple differentiation steps in vivo are more similar to each other. These data suggest that most of the random allele-specific stable transcriptional states on autosomal chromosomes are established de novo during cell lineage differentiation. Given that allele-specific transcriptional states are more stable in cells not undergoing extensive differentiation than in the clones we assessed after full lineage differentiation in vivo, we introduce the “Punctuated Disequilibria” model: random allelic expression biases are stable if the cells are not undergoing differentiation, but may change during differentiation between developmental stages and reach a new stable equilibrium that will only be challenged if the cell engages in further differentiation. Thus, the transcriptional allelic states may not be a stable feature of the differentiating clone, but phenotypic diversity between clones of a population at any given stage of the cell lineage is still ensured.
Detecting quantitative trait loci and exploring chromosomal pairing in autopolyploids usingpolyqtlR
Authors: Bourke Peter M. , Voorrips Roeland E. , Hackett Christine A. , van Geest Geert , Willemsen Johan H. , Arens Paul , Smulders Marinus J. M. , Visser Richard G. F. , Maliepaard Chris 
Published: June 2021

AbstractMotivationThe investigation of quantitative trait loci (QTL) is an essential component in our understanding of how organisms vary phenotypically. However, many important crop species are polyploid (carrying more than two copies of each chromosome), requiring specialised tools for such analyses. Moreover, deciphering meiotic processes at higher ploidy levels is not straightforward, but is necessary to understand the reproductive dynamics of these species, or uncover potential barriers to their genetic improvement.ResultsHere we presentpolyqtlR, a novel software tool to facilitate such analyses in (auto)polyploid crops. It performs QTL interval mapping in F1populations of outcrossing polyploids of any ploidy level using identity-by-descent (IBD) probabilities. The allelic composition of discovered QTL can be explored, enabling favourable alleles to be identified and tracked in the population. Visualisation tools within the package facilitate this process, and options to include genetic co-factors and experimental factors are included. Detailed information on polyploid meiosis including prediction of multivalent pairing structures, detection of preferential chromosomal pairing and location of double reduction events can be performed.Availability and implementationpolyqtlRis freely available from the Comprehensive R Archive Network (CRAN) athttp://cran.r-project.org/package=polyqtlR.Contactpeter.bourke@wur.nlorchris.maliepaard@wur.nlSupplementary informationSupplementary data are available
ARID1A loss derepresses human endogenous retrovirus-H to modulate BRD4-dependent transcription
Authors: Yu Chunhong , Lei Xiaoyun , Chen Fang , Mao Song , Lv Lu , Liu Honglu , Hu Xueying , Wang Runhan , Shen Licong , Zhang Na , Meng Yang , Shen Yunfan , Li Pishun , Huang Shi , Shao Hao , Lin Changwei , Zhang Zhuohua , Yuan Kai 
Published: June 2021

AbstractThe transposable elements (TEs) through evolutionary exaptation have become an integral part of human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis are recognized, their role in malignancy has only started to emerge. Here we show that many TEs, especially the pluripotency-related endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. The transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors including ARID1A. Knockout of ARID1A in CRC cells leads to increased accessibility at HERVH loci and enhanced transcription, which is dependent on ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulate their dynamics, and co-regulate many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, which can promote tumorigenesis by stimulating BRD4-dependent transcription when ARID1A is mutated.
Tumor Necrosis Factor induces pathogenic programmed macrophage necrosis in
tuberculosis through a mitochondrial-lysosomal-endoplasmic reticulum
circuit
Authors: Roca Francisco J. , Redmond Sarah , Ramakrishnan Lalita 
Published: June 2021

SUMMARY
Necrosis of infected macrophages constitutes a critical pathogenetic event
in tuberculosis releasing mycobacteria into the extracellular environment where
they can grow unrestricted. In zebrafish infected with
Mycobacterium marinum, a close relative of
Mycobacterium tuberculosis, excess Tumor Necrosis
Factor triggers programmed necrosis of infected macrophages through the
production of mitochondrial reactive oxygen species (ROS) and the participation
of cyclophilin D, a component of the mitochondrial permeability transition pore.
Here we show that this necrosis pathway is not mitochondrion-intrinsic but
rather results from an interorganellar circuit initiating and culminating in the
mitochondrion. Mitochondrial ROS induce production of lysosomal ceramide which
ultimately activates the cytosolic protein BAX. BAX promotes calcium flow from
the endoplasmic reticulum into the mitochondrion through ryanodine receptors.
The resultant mitochondrial calcium overload triggers cyclophilin D-mediated
necrosis. We identify ryanodine receptors and plasma membrane L-Type calcium
channels as specific druggable targets to intercept mitochondrial calcium
overload so as to inhibit macrophage necrosis.
How does ambidextrous leadership promote innovation in project-based construction companies? Through mediating role of knowledge-sharing and moderating role of innovativeness
Authors: Haider Syed Arslan , Zubair Muhammad , Tehseen Shehnaz , Iqbal Shahid , Sohail Mariam 
Published: June 2021

PurposeResearch on adopting leadership style like ambidextrous leadership to enhance employees' innovative work behavior (IWB) is in an initial stage. Moreover, employees need a high knowledge sharing attitude to show more IWB. The purpose of this study is to empirically test the impact of ambidextrous leadership on IWB with the mediating role of knowledge sharing and the moderating role of innovativeness as a project requirement (IAPR).Design/methodology/approachThe simple random sampling technique was used to collect data from 542 employees of project-based construction companies operating in Pakistan. Smart partial least squares-structural equation modeling (Smart PLS SEM v.3.2.8) was used to test the hypotheses.FindingsThe result revealed that ambidextrous leadership has a significant and positive effect on knowledge sharing but negative effect on IWB at the workplace. Additionally, the mediating role of knowledge sharing has been tested and proved to be a potential mediator between ambidextrous leadership and IWB. Also, IAPR as moderator has a significant and positive effect on knowledge sharing and IWB.Practical implicationsThe managers need to develop an ambidexterity-oriented strategy and communicate this strategy across the members of the whole organization. These processes can be facilitated by ambidextrous leaders with complex behavioral repertoires and specific constellations and characteristics of top management teams.Originality/valueThe relationship between ambidextrous leadership and IWB is the new contribution through the mediating of knowledge sharing between AL and IWB also moderation role IWB between knowledge sharing and IWB.
“I played a song with the help of a magic banana”: assessing short-term making events
Authors: Nixon Jessie , Halverson Erica , Stoiber Andy , Garbacz Andy 
Published: June 2021

Purpose
The purpose of this study is to understand how learners describe their experiences with short-term, introductory maker experiences and to test a method for assessing learners’ experiences authentic to short-term learning.

Design/methodology/approach
The authors collected written responses from participants at a two-day event, STEM Center Learning Days. Through an analysis of 707 unique instances of learner responses to participation in drop-in maker activities, they examined how participants describe their short-term learning experiences.

Findings
The authors found that although some activities appear to onlookers to create passive experiences for learners, these seemingly passive moments have a significant impact on learners. In addition, some learners described themselves as working in tandem with tools to make something work and other learners viewed the tools as working autonomously. They found that the assessment method allowed them to gain an understanding of how learners describe their experiences offering important implications for understanding short-term learning events.

Originality/value
The findings provide researchers studying short-term learning in its natural setting a new method to understand how learners make sense of their individual experience. Further, designers of short-term learning experiences may gain insights into their unique activities and indications of where additional guidance and scaffolds will improve small learning moments.
Neo-rural small entrepreneurs’ motivations and challenges in Portugal’s low density regions
Authors: Dal Bello Ubyrajara Brasil , Marques Carla , Sacramento Octávio , Galvão Anderson 
Published: June 2021

Purpose
This study sought to fill a gap in the literature by examining the dynamics of neo-rural small entrepreneurs’ business activities as little research has been done on these individuals. The research was conducted in three of Portugal’s low density territories (i.e. Miranda do Douro, Penamacor and Aljezur), focusing on understanding these outsider entrepreneurs’ main motivations and challenges after they decide to leave the city to settle in rural areas and become small business owners.

Design/methodology/approach
Data were collected in semi-structured interviews with 26 neo-rural entrepreneurs. The multiple-case study method was applied to assess the differences and similarities between the interviewees and their respective contexts. NVivo 11.0 software was used to conduct content analysis.

Findings
The results reveal that rural environments appear to attract these new entrepreneurs for various reasons, such as taking advantage of business opportunities, searching for a better quality of life and responding to family needs. The multiple motives contributing to the need for change and entrepreneurship fit well within social cognitive theory. However, these individuals subsequently experience difficulties related mainly to a lack of infrastructure, little preexisting knowledge, a need for financial capital and the absence of the right workforce.

Originality/value
The findings on the experiences, difficulties and challenges of neo-rural entrepreneurs constitute new contributions because few existing studies have concentrated on migration and/or immigration entrepreneurship in rural contexts. The results can serve as a starting point for other similar studies.
Authenticity, local creatives and place branding: a case study from the Blue Mountains, Australia
Authors: Sandbach Katrina 
Published: June 2021

PurposeThis paper discusses the notion of authenticity and the role of local creatives in the place branding process based on a case study of Mtns Made, a brand for the creative industries in the Blue Mountains of Sydney, Australia. This paper aims to examine the development, implementation and management of a place brand from the ground-up and explore the implications for a situated place branding practice.Design/methodology/approachThe concept of brand culture was used as a theoretical lens to view place branding. A qualitative case study approach was taken, incorporating the collection of primary and secondary documents, observation of online platforms and real-world events, field notes and personal reflection from an insider position.FindingsThe findings of this study suggest that local creatives can and have played a central role in place branding. The study also illustrates a model for place branding that centres on stakeholder participation in an ongoing process.Originality/valueLocal culture and creativity are largely viewed as assets for place branding; this paper draws attention to the agency of local creatives in the place branding process. This study offers three pillars of place brand authenticity and establishes a framework for place brand analysis based on a branding design strategy.
Unravelling the differential effects of pride and guilt along with values on green intention through environmental concern and attitude
Authors: Mukherjee Bidhan , Chandra Bibhas 
Published: June 2021

PurposeIn response to scholarly calls, the study aims to extend and magnify the existing understanding by unravelling the differential impact of anticipated emotions on green practice adoption intention through a proposed model by integrating anticipated pride and guilt in the same continuum along with values (altruistic, biospheric and egoistic) on an employee's attitude.Design/methodology/approachA self-administered questionnaire was used to collect data randomly from 307 employees and middle-level executives of three subsidiaries of CIL through the simple random sampling (SRS) technique. Data were analysed using structural equation modelling (SEM).FindingsResults demonstrate that anticipated guilt influences individual cognitions and future ecological decision-making through improved attitude and higher concern for the environment while pride influences only through improved attitude. Other than biospheric and altruistic values, anticipated guilt is a direct and important antecedent of concern. Altruistic values are more influential predictors of environmental intentions in comparison to biospheric values. At the same time, environmental concern is more robust in predicting eco-intentions than attitude.Originality/valueIt makes notable difference from other studies by not only exploring the validity of the relationship between values on attitude and environmental concern but has also considered anticipated emotions of pride and guilt together alongside values on the same continuum as an antecedent of environmental attitude and concern towards employees’ green behavioural intention at the workplace. The findings are believed to provide a common consensus on differential effects of different states of emotions on environmental concern and attitude.