bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of glycosylation on a broad-spectrum vaccine against SARS-CoV-2
Authors: Huang Han-Yi , Liao Hsin-Yu , Chen Xiaorui , Wang Szu-Wen , Cheng Cheng-Wei , Shahed-Al-Mahmud Md. , Chen Ting-Hua , Lo Jennifer M. , Liu Yo-Min , Wu Yi-Min , Ma Hsiu-Hua , Chang Yi-Hsuan , Tsai Ho-Yang , Chou Yu-Chi , Hsueh Yi-Ping , Tsai Ching-Yen , Huang Pau-Yi , Chang Sui-Yuan , Chao Tai-Ling , Kao Han-Chieh , Tsai Ya-Min , Chen Yen-Hui , Wu Chung-Yi , Jan Jia-Tsrong , Cheng Ting-Jen Rachel , Lin Kuo-I , Ma Che , Wong Chi-Huey 
Published: May 2021

AbstractA major challenge to end the pandemic caused by SARS-CoV-2 is to develop a broadly protective vaccine. As the key immunogen, the spike protein is frequently mutated with conserved epitopes shielded by glycans. Here, we reveal that spike glycosylation has site-differential effects on viral infectivity and lung epithelial cells generate spike with more infective glycoforms. Compared to the fully glycosylated spike, immunization of spike protein with N-glycans trimmed to the monoglycosylated state (Smg) elicits stronger immune responses and better protection for hACE2 transgenic mice against variants of concern. In addition, a broadly neutralizing monoclonal antibody was identified from the Smg immunized mice, demonstrating that removal of glycan shields to better expose the conserved sequences is an effective and simple approach to broad-spectrum vaccine development.One-Sentence SummaryRemoving glycan shields to expose conserved epitopes is an effective approach to develop a broad-spectrum SARS-CoV-2 vaccine.
The RIFF: an automated environment for studying the neural basis of auditory-guided complex behavior
Authors: Jankowski Maciej M. , Polterovich Ana , Kazakov Alex , Niediek Johannes , Nelken Israel 
Published: May 2021

AbstractBehavior consists of the interaction between an organism and its environment, and is controlled by the brain. Brain activity varies at sub-second time scales, but behavioral measures are usually coarse (often consisting of only binary trial outcomes). To overcome this mismatch, we developed the RIFF: a programmable interactive arena for freely-moving rats with multiple feeding areas, multiple sound sources, high-resolution behavioral tracking, and simultaneous electrophysiological recordings. We describe two complex tasks implemented in the RIFF. Rats quickly learned these tasks and developed anticipatory behavior. Neurons in auditory cortex and posterior insula showed sensitivity to non-auditory parameters such as location and pose. Our combination of wireless electrophysiology and detailed behavioral documentation in a controlled environment produces insights into the cognitive capabilities and learning mechanisms of rats and opens the way to a better understanding of how brains control behavior.
Diffusion and interaction dynamics of the cytosolic peroxisomal import receptor PEX5
Authors: Galiani S , Reglinski K , Carravilla P , Barbotin A , Urbančič I , Ott J , Sehr J , Sezgin E , Schneider F , Waithe D , Hublitz P , Schliebs W , Erdmann R , Eggeling C 
Published: May 2021

AbstractMeasuring diffusion dynamics in living cells is essential for the understanding of molecular interactions. While various techniques have been used to explore such characteristics in the plasma membrane, this is less developed for measurements inside the cytosol. An example of cytosolic action is the import of proteins into peroxisomes, via the peroxisomal import receptor PEX5. Here, we combined advanced microscopy and spectroscopy techniques such as fluorescence correlation spectroscopy (FCS) and super-resolution STED microscopy to present a detailed characterization of the diffusion and interaction dynamics of PEX5. Among other features, we disclose a slow diffusion of PEX5, independent of aggregation or target binding, but associated with cytosolic interaction partners via its N-terminal domain. This sheds new light on the functionality of the receptor in the cytosol. Besides specific insights, our study highlights the potential of using complementary microscopy tools to decipher molecular interactions in the cytosol via studying their diffusion dynamics.SummaryThe peroxisomal import receptor PEX5 transports newly synthesized proteins from the cytosol to the peroxisomal matrix. Here the cytosolic diffusion and interaction dynamics of PEX5 are characterized by advanced microscopic spectroscopy methods, revealing a so far unknown interaction partner.
Plasticity of olfactory bulb inputs mediated by dendritic NMDA-spikes in piriform cortex
Authors: Kumar Amit , Barkai Edi , Schiller Jackie 
Published: May 2021

AbstractThe piriform cortex (PCx) is essential for learning of odor information. The current view postulates odor learning in the PCx is mainly due to plasticity in intracortical (IC) synapses, while odor information from the olfactory bulb carried via the lateral olfactory tract (LOT) is “hardwired”. Here we revisit this notion by studying location and pathway dependent plasticity rules. We find that in contrast to the prevailing view, synaptic and optogenetically activated LOT synapses undergo strong and robust long-term potentiation (LTP) mediated by only few local NMDA-spikes delivered at theta frequency, while global spike timing dependent plasticity protocols (STDP) failed to induce LTP in these distal synapses. An inverse result was observed for more proximal apical IC synapses; they undergo plasticity with STDP but are refractive to local NMDA-spike protocols. These results are consistent with a self-potentiating mechanism of odor information via NMDA-spikes which can form branch-specific memory traces of odors.
Force and stepwise movements of gliding motility in human pathogenic bacterium Mycoplasma pneumoniae
Authors: Mizutani Masaki , Sasajima Yuya , Miyata Makoto 
Published: May 2021

ABSTRACTMycoplasma pneumoniae, a human pathogenic bacterium, binds to sialylated oligosaccharides and glides on host cell surfaces via a unique mechanism. Gliding motility is essential for initiating the infectious process. In the present study, we measured the stall force of an M. pneumoniae cell carrying a bead that was manipulated using optical tweezers on two strains. The stall forces of M129 and FH strains were averaged to be 23.7 and 19.7 pN, respectively, much weaker than those of other bacterial surface motilities. The binding activity and gliding speed of the M129 strain on sialylated oligosaccharides were eight and two times higher than those of the FH strain, respectively, showing that binding activity is not linked to gliding force. Gliding speed decreased when cell binding was reduced by addition of free sialylated oligosaccharides, indicating the existence of a drag force during gliding. We detected stepwise movements, likely caused by a single leg under 0.2–0.3 mM free sialylated oligosaccharides. A step size of 14–19 nm showed that 25–35 propulsion steps per second are required to achieve the usual gliding speed. The step size was reduced to less than half with the load applied using optical tweezers, showing that a 2.5 pN force from a cell is exerted on a leg. The work performed in this step was 16%–30% of the free energy of the hydrolysis of ATP molecules, suggesting that this step is linked to the elementary process of M. pneumoniae gliding.IMPORTANCEHuman mycoplasma pneumonia is caused by the bacterium Mycoplasma pneumoniae. This tiny bacterium, shaped like a missile, binds to human epithelial surfaces and spreads using a unique gliding mechanism to establish infection. Here, we analyzed the movements and force of this motility using a special setup: optical tweezers. We then obtained detailed mechanical data to understand this mechanism. Furthermore, we succeeded in detecting small steps of nanometers in its gliding, which is likely linked to the elementary process of the core reaction: chemical to mechanical energy conversion. These data provide critical information to both control this human pathogen and explore new ideas for artificial molecular machines.
Loss of Resf1 reduces the efficiency of embryonic stem cell self-renewal and germline entry
Authors: Vojtek Matúš , Chambers Ian 
Published: May 2021

SummaryRetroelement silencing factor 1 (RESF1) interacts with the key regulators of mouse embryonic stem cells (ESCs) OCT4 and NANOG, and its absence results in sterility of mice. However, the function of RESF1 in ESCs and germ line specification is poorly understood. In this study, we used Resf1 knockout cell lines to determine the requirements of RESF1 for ESCs self-renewal and for in vitro specification of ESCs into primordial germ cell-like cells (PGCLCs). We found that deletion of Resf1 in ESCs cultured in serum and LIF reduces self-renewal potential whereas episomal expression of RESF1 has a modest positive effect on ESC self-renewal. In addition, RESF1 is not required for the capacity of NANOG and its downstream target ESRRB to drive self-renewal in the absence of LIF. However, Resf1 deletion reduces efficiency of PGCLC differentiation in vitro. These results identify Resf1 as a novel player in the regulation of pluripotent stem cells and germ cell specification.
spatzie: An R package for identifying significant transcription factor motif co-enrichment from enhancer-promoter interactions
Authors: Hammelman Jennifer , Krismer Konstantin , Gifford David K. 
Published: May 2021

AbstractGenomic interactions provide important context to our understanding of the state of the genome. One question is whether specific transcription factor interactions give rise to genome organization. We introduce spatzie, an R package and a website that implements statistical tests for significant transcription factor motif cooperativity between enhancer-promoter interactions. We conducted controlled experiments under realistic simulated data from ChIP-seq to confirm spatzie is capable of discovering co-enriched motif interactions even in noisy conditions. We then use spatzie to investigate cell type specific transcription factor cooperativity within recent human ChIA-PET enhancer-promoter interaction data. The method is available online at https://spatzie.mit.edu.
A photo-switchable yeast isocitrate dehydrogenase to control metabolic flux through the citric acid cycle
Authors: Chen Haoqi , Mulder Lianne , Wijma Hein J. , Wabeke Ronja , Losa Jose Pedro Vila Cha , Rovetta Mattia , de Leeuw Tijn Caspar , Millias-Argeitis Andreas , Heinemann Matthias 
Published: May 2021

AbstractFor various research questions in metabolism, it is highly desirable to have means available, with which the flux through specific pathways can be perturbed dynamically, in a reversible manner, and at a timescale that is consistent with the fast turnover rates of metabolism. Optogenetics, in principle, offers such possibility. Here, we developed an initial version of a photo-switchable isocitrate dehydrogenase (IDH) aimed at controlling the metabolic flux through the citric acid cycle in budding yeast. By inserting a protein-based light switch (LOV2) into computationally identified active/regulatory-coupled sites of IDH and by using in vivo screening in Saccharomyces cerevisiae, we obtained a number of IDH enzymes whose activity can be switched by light. Subsequent in-vivo characterization and optimization resulted in an initial version of photo-switchable (PS) IDH. While further improvements of the enzyme are necessary, our study demonstrates the efficacy of the overall approach from computational design, via in vivo screening and characterization. It also represents one of the first few examples, where optogenetics were used to control the activity of a metabolic enzyme.
Conformational Changes of RORγ During Response Element Recognition and Coregulator Engagement
Authors: Strutzenberg Timothy S. , Novick Scott J. , Garcia-Ordonez Ruben D. , Doebelin Christelle , He Yuanjun , Chang Mi Ra , Kamenecka Theodore M. , Griffin Patrick R. 
Published: May 2021

ABSTRACTThe retinoic acid receptor-related orphan receptor γ (RORγ) is a ligand-dependent transcription factor of the nuclear receptor super family that underpins metabolic activity, immune function, and cancer progression. Despite being a valuable drug target in health and disease, our understanding of the ligand-dependent activities of RORγ is far from complete. Like most nuclear receptors, RORγ must recruit coregulatory protein to enact the RORγ target gene program. To date, a majority of structural studies have been focused exclusively on the RORγ ligand-binding domain and the ligand-dependent recruitment of small peptide segments of coregulators. Herein, we examine the ligand-dependent assembly of full length RORγ:coregulator complexes on cognate DNA response elements using structural proteomics and small angle x-ray scattering. The results from our studies suggest that RORγ becomes elongated upon DNA recognition, preventing long range interdomain crosstalk. We also determined that the DNA binding domain adopts a sequence-specific conformation, and that coregulatory proteins may be able to ‘sense’ the ligand- and DNA-bound status of RORγ. We propose a model where ligand-dependent coregulator recruitment may be influenced by the sequence of the DNA to which RORγ is bound. Overall, the efforts described herein will illuminate important aspects of full length RORγ and monomeric orphan nuclear receptor target gene regulation through DNA-dependent conformational changes.GRAPHICAL ABSTRACT
Phosphatidylinositol 3-kinase-independent synthesis of PtdIns(3,4)P2 by a phosphotransferase
Authors: Walpole Glenn F. W. , Pacheco Jonathan , Chauhan Neha , Abbas Yazan M. , Montaño-Rendón Fernando , Liu Zetao , Zhu Hongxian , Brumell John H. , Deiters Alexander , Hammond Gerald R.V. , Grinstein Sergio , Fairn Gregory D. 
Published: May 2021

AbstractDespite their comparatively low abundance, phosphoinositides play a central role in membrane traffic and signalling. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 are uniquely important, as they promote cell growth, survival, and migration. Pathogenic organisms have developed means to subvert phosphoinositide metabolism to promote successful infection and their survival within host organisms. We demonstrate that PtdIns(3,4)P2 is generated in host cells by effectors of the enteropathogenic bacteria Salmonella and Shigella. Pharmacological, gene silencing and heterologous expression experiments revealed that, remarkably, the biosynthesis of PtdIns(3,4)P2 occurs independently of phosphoinositide 3-kinases. Instead, we found that the Salmonella effector SopB, heretofore believed to be a phosphatase, generates PtdIns(3,4)P2de novo via a phosphotransferase/phosphoisomerase mechanism. Recombinant SopB is capable of generating PtdIns(3,4)P2 from PtdIns(4,5)P2 in a cell-free system. Through a remarkable instance of convergent evolution, bacterial effectors acquired the ability to synthesize 3-phosphorylated phosphoinositides by an ATP- and kinase-independent mechanism, thereby subverting host signaling to gain entry and even provoke oncogenic transformation.
Distinct allosteric mechanisms of first-generation MsbA inhibitors
Authors: Thélot François A. , Zhang Wenyi , Song KangKang , Xu Chen , Huang Jing , Liao Maofu 
Published: May 2021

AbstractPresent in all kingdoms of life, ATP-binding cassette (ABC) transporters couple ATP hydrolysis to mechanical force and facilitate trafficking of diverse substrates across biological membranes. Although many ABC transporters are promising drug targets, their mechanisms of regulation by small molecule inhibitors remain largely unknown. Herein, we used the lipopolysaccharide (LPS) flippase MsbA, a prototypical ABC exporter, as a model system to probe mechanisms of allosteric modulation by compounds binding to the transmembrane domains (TMDs). Recent chemical screens have identified intriguing LPS transport inhibitors targeting MsbA: the ATPase stimulator TBT1 and the ATPase inhibitor G247. Despite preliminary biochemical and structural data, it is unclear how TBT1 and G247 bind to the MsbA TMDs yet induce opposite allosteric effect in the nucleotide-binding domains (NBDs). Through single-particle EM, mutagenesis and activity assay, we show that TBT1 and G247 bind adjacent yet separate locations in the TMDs, inducing drastic changes in TMD conformation and NBD positioning. Two TBT1 molecules asymmetrically occupy the LPS binding site to break the symmetry of MsbA, resulting in disordered transmembrane helices and decreased NBD distance. In this novel inhibited ABC transporter state, decreased distance between the NBDs causes stimulation of ATP hydrolysis yet LPS transport blockage. In contrast, G247 acts as a TMDs wedge, symmetrically increasing NBD separation and preventing conformational transition of MsbA. Our study uncovers the distinct mechanisms of the first-generation MsbA-specific inhibitors and demonstrates that rational design of substrate-mimicking compounds can be exploited to develop useful ABC transporter modulators.
Applying sentiment analytics to examine social media crises: a case study of United Airline's crisis in 2017
Authors: Tian Xin , He Wu , Wang Feng-Kwei 
Published: May 2021

PurposeIn recent years, social media crises occurred more and more often, which negatively affect the reputations of individuals, businesses and communities. During each crisis, numerous users either participated in online discussion or widely spread crisis-related information to their friends and followers on social media. By applying sentiment analysis to study a social media crisis of airline carriers, the purpose of this research is to help companies take measure against social media crises.Design/methodology/approachThis study used sentiment analytics to examine a social media crisis related to airline carriers. The arousal, valence, negative, positive and eight emotional sentiments were applied to analyze social media data collected from Twitter.FindingsThis research study found that social media sentiment analysis is useful to monitor public reaction after a social media crisis arises. The sentiment results are able to reflect the development of social media crises quite well. Proper and timely response strategies to a crisis can mitigate the crisis through effective communication with the customers and the public.Originality/valueThis study used the Affective Norms of English Words (ANEW) dictionary to classify the words in social media data and assigned the words with two elements to measure the emotions: valence and arousal. The intensity of the sentiment determines the public reaction to a social media crisis. An opinion-oriented information system is proposed as a solution for resolving a social media crisis in the paper.
Leadership on the run: time management among deputy ministers in Canada
Authors: Dutil Patrice , Migone Andrea Riccardo 
Published: May 2021

PurposeThe authors examine the time allocation and management of deputy ministers (DMs) in Canada.Design/methodology/approachThe authors analyze the results from a 2020 survey of DMs.FindingsThe authors observe that, like private sector leaders, DMs work very long hours and tend to allocate their time fairly consistently across functions. Nevertheless, important differences exist particularly depending on the size of their department.Research limitations/implicationsWhile a substantial percentage of answers were returned, these skew toward provincial rather than federal public servants and not all jurisdictions are equally represented.Practical implicationsThe distribution of areas of focus for DMs and their time allocation differences speak to potentially important discussions to be had in time management practice.Originality/valueThis is the first and only analysis of time management for senior public service executives based on a survey instrument.
What citizens experience and how omni-channel could help–insights from a building permit case
Authors: Schenk Birgit , Dolata Mateusz , Schwabe Christiane , Schwabe Gerhard 
Published: May 2021

PurposeBy increasing the digitalization of commercial services citizens' expect more from public services. First of all, this study will strive to identify which problems citizens encounter when they use a complex public service: preparation of an application for a building permit. In the light of the popularity of omnichannel approaches, the study then explores how omni-channel could help to address the problems which have been identified.Design/methodology/approachWe implement the first phases of an action design science research project. We collect data both from citizens and public agencies and frame them as transparency problems. These abstract problems are then addressed by an omnichannel service provision as an abstract solution. The abstract solution is then instantiated in a design in the form of a user scenario developed in collaboration with current and future public officials.FindingsThe analysis uncovers multiple transparency issues: it distinguishes between process, case, language, cross-channel and cost transparency. One root cause of the transparency issues observed is the lack of service transparency which defines the purpose and scope of a ser-vice. We therefore recommend defining a service-strategy before informational and technical aspects of an omnichannel approach can be implemented. Following this strategy, omnichannel offers public administrations unique opportunities to excel in citizens' service provision.Originality/valueThe study provides insights into how citizens view complex public services. For researchers, this study offers the conceptualization as transparency issues. Practitioners from the public administrations can also benefit from the concept and vision of omnichannel public services.
The effect of social media use on empathy and welling: a personality perspective in Saudi Arabia
Authors: Albashrawi Mousa , Asiri Yousef , Binsawad Muhammad , Alqahtani Latifah 
Published: May 2021

Purpose
The purpose of this study is to explore the impact of social media use on both empathy and well-being through using a five-factor model (FFM) of personality in the context of Saudi Arabia.

Design/methodology/approach
Data were collected from the 13 regions in Saudi Arabia. Confirmatory factor analysis was used to measure the reliability and validity of the study’s constructs and a structural equation modeling technique was applied to test the study hypotheses.

Findings
With a sample of 450 users, the regression results indicate a less significant relationship between personality and social media use, as well as between personality and affective empathy, while a more significant relationship between personality and cognitive empathy. Also, individuals’ well-being are influenced directly by the heavy use of social media.

Research limitations/implications
The cross-sectional design used in this research may not be able to provide the true essence of the hypothesized relationships compared to the cause-effect design. This study furthers the understanding of the role of personality on empathy and well-being in social media among Saudis from one side and provides insights to professionals for better improvement of social media and so better individuals’ well-being from the other side.

Originality/value
This paper fills an untapped gap in a developing country context by exploring the relationship between the usage of social media and the two dimensions of empathy, which, in turn, influence well-being under the theoretical lens of an FFM personality.