bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial CaMKII causes metabolic reprogramming, energetic insufficiency, and dilated cardiomyopathy
Authors: Luczak Elizabeth D. , Wu Yuejin , Granger Jonathan M. , Joiner Mei-ling A. , Wilson Nicholas R. , Gupta Ashish , Umapathi Priya , Murphy Kevin R. , Reyes Gaido Oscar E. , Sabet Amin , Corradini Eleonora , Wang Yibin , Heck Albert J.R. , Wei An-Chi , Weiss Robert G. , Anderson Mark E. 
Published: February 2020

AbstractDespite the clear association between myocardial injury, heart failure and depressed myocardial energetics, little is known about upstream signals responsible for remodeling myocardial metabolism after pathological stress. We found increased mitochondrial calmodulin kinase II (CaMKII) activation and left ventricular dilation in mice one week after myocardial infarction (MI) surgery. In contrast, mice with genetic mitochondrial CaMKII inhibition were protected from left ventricular dilation and dysfunction after MI. Mice with myocardial and mitochondrial CaMKII over-expression (mtCaMKII) had severe dilated cardiomyopathy and decreased ATP that caused elevated cytoplasmic resting (diastolic) Ca2+concentration and reduced mechanical performance. We mapped a metabolic pathway that allowed us to rescue disease phenotypes in mtCaMKII mice, providing new insights into physiological and pathological metabolic consequences of CaMKII signaling in mitochondria. Our findings suggest myocardial dilation, a disease phenotype lacking specific therapies, can be prevented by targeted replacement of mitochondrial creatine kinase, or mitochondrial-targeted CaMKII inhibition.
A trans-eQTL network regulates osteoclast multinucleation and bone mass
Authors: Pereira Marie , Ko Jeong-Hun , Logan John , Protheroe Hayley , Kim Kee-Beom , Tan Amelia Li Min , Park Kwon-Sik , Rotival Maxime , Petretto Enrico , Bassett J. H. Duncan , Williams Graham R. , Behmoaras Jacques 
Published: February 2020

AbstractFunctional characterisation of cell-type specific regulatory networks is key to establish a causal link between genetic variation and phenotype. The osteoclast offers a unique model for interrogating the contribution of co-regulated genes toin vivophenotype as its multinucleation and resorption activities determine quantifiable skeletal traits. Here we took advantage of atrans-regulated gene network (MMnet, macrophage multinucleation network) which we found to be significantly enriched for GWAS variants associated with bone-related phenotypes. We found that the network hub geneBcat1and seven other co-regulated MMnet genes out of 13, regulate bone function. Specifically, global (Pik3cb−/−,Atp8b2+/−,Igsf8−/−,Eml1−/−,Appl2−/−,Deptor−/−) and myeloid-specificSlc40a1ΔLysMCreknockout mice displayed abnormal bone phenotypes. We report antagonizing effects of MMnet genes on bone mass in mice and osteoclast multinucleation/resorption in humans with strong correlation between the two. These results identify MMnet as a functionally conserved network that regulates osteoclast fusion and bone mass.Impact statementWe took advantage of the osteoclast whose multinucleation properties correlate with bone mass. We show that atrans-regulated gene network (MMnet) controls skeletal homeostasis through osteoclast multinucleation and function.
New functional identity of the essential inner membrane protein YejM: the cardiolipin translocator is also a metalloenzyme
Authors: Gabale Uma , Peña Palomino Perla A. , Kim HyunAh , Chen Wenya , Ressl Susanne 
Published: February 2020

AbstractRecent recurrent outbreaks of Gram-negative bacteria show the critical need to target essential bacterial mechanisms to fight the increase of antibiotic resistance. Pathogenic Gram-negative bacteria have developed several strategies to protect themselves against the host immune response and antibiotics. One strategy is to remodel the outer membrane where several genes are involved.yejMwas discovered as an essential gene inE. coliandS. typhimuriumthat plays a critical role in their virulence by changing the outer membrane permeability by translocating and increasing the cardiolipin lipid concentration. How the inner membrane protein YejM with its periplasmic domain acts as a cardiolipin translocator remains unknown. Despite overwhelming structural similarity of the periplasmic domains of two YejM homologues with hydrolases like arylsulfatases, no enzymatic activity has been reported for YejM. Our studies reveal an intact active site with bound metal ions in the structure of YejM periplasmic domain. Furthermore, we show that YejM has a phosphatase activity that is dependent on the presence of magnesium ions and is linked to its cardiolipin translocation properties. Understanding the molecular mechanism by which YejM is involved in OM remodeling will help to identify a new drug target in the fight against the increased antibiotic resistance.
Delay-period activity in frontal, parietal, and occipital cortex tracks different attractor dynamics in visual working memory
Authors: Yu Qing , Panichello Matthew F. , Cai Ying , Postle Bradley R. , Buschman Timothy J. 
Published: February 2020

AbstractOne important neural hallmark of working memory is persistent elevated delay-period activity in frontal and parietal cortex. In human fMRI, delay-period BOLD activity in frontal and parietal cortex increases monotonically with memory load and asymptotes at an individual’s capacity. Previous work has demonstrated that frontal and parietal delay-period activity correlates with the decline in behavioral memory precision observed with increasing memory load. However, because memory precision can be influenced by a variety of factors, it remains unclear what cognitive processes underlie persistent activity in frontal and parietal cortex. Recent psychophysical work has shown that attractor dynamics bias memory representations toward a few stable representations and reduce the effects of internal noise. From this perspective, imprecision in memory results from both drift towards stable attractor states and random diffusion. Here we asked whether delay-period BOLD activity in frontal and parietal cortex might be explained, in part, by these attractor dynamics. We analyzed data from an existing experiment in which subjects performed delayed recall for line orientation, at different loads, during fMRI scanning. We modeled subjects’ behavior using a discrete attractor model, and calculated within-subject correlation between frontal and parietal delay-period activity and estimated sources of memory error (drift and diffusion). We found that although increases in frontal and parietal activity were associated with increases in both diffusion and drift, diffusion explained the most variance in frontal and parietal delay-period activity. In comparison, a subsequent whole-brain regression analysis showed that drift rather than diffusion explained the most variance in delay-period activity in lateral occipital cortex. These results provide a new interpretation for the function of frontal, parietal, and occipital delay-period activity in working memory.
Gene tree discord, simplex plots, and statistical tests under the coalescent
Authors: Allman Elizabeth S. , Mitchell Jonathan D. , Rhodes John A. 
Published: February 2020

AbstractA simple graphical device, the simplex plot of quartet concordance factors, is introduced to aid in the exploration of a collection of gene trees on a common set of taxa. A single plot summarizes all gene tree discord, and allows for visual comparison to the expected discord from the multispecies coalescent model (MSC) of incomplete lineage sorting on a species tree. A formal statistical procedure is described that can quantify the deviation from expectation for each subset of four taxa, suggesting when the data is not in accord with the MSC, and thus either gene tree inference error is substantial or a more complex model such as that on a network may be required. If the collection of gene trees appears to be in accord with the MSC, the plots may reveal when substantial incomplete lineage sorting is present and coalescent based species tree inference is preferred over concatenation approaches. Applications to both simulated and empirical multilocus data sets illustrate the insights provided.
Increased metal tolerance and bioaccumulation of zinc and cadmium in Chlamydomonas reinhardtii expressing a AtHMA4 C-terminal domain protein
Authors: Ibuot Aniefon , Webster Rachel E. , Williams Lorraine E. , Pittman Jon K. 
Published: February 2020

AbstractThe use of microalgal biomass for metal pollutant bioremediation might be improved by genetic engineering to modify the selectivity or capacity of metal biosorption. A plant cadmium (Cd) and zinc (Zn) transporter (AtHMA4) was used as a transgene to increase the ability of Chlamydomonas reinhardtii to tolerate 0.2 mM Cd and 0.3 mM Zn exposure. The transgenic cells showed increased accumulation and internalisation of both metals compared to wild type. AtHMA4 was expressed either as the full-length protein or just the C-terminal tail, which is known to have metal binding sites. Similar Cd and Zn tolerance and accumulation was observed with expression of either the full-length protein or C-terminal domain, suggesting that enhanced metal tolerance was mainly due to increased metal binding rather than metal transport. The effectiveness of the transgenic cells was further examined by immobilisation in calcium alginate to generate microalgal beads that could be added to a metal contaminated solution. Immobilisation maintained metal tolerance, while AtHMA4-expressing cells in alginate showed a concentration-dependent increase in metal biosorption that was significantly greater than alginate beads composed of wild type cells. This demonstrates that expressing AtHMA4 full-length or C-terminus has great potential as a strategy for bioremediation using microalgal biomass.
Comparison of protein and peptide fractionation approaches in protein identification and quantification fromSaccharomyces cerevisiae
Authors: Deng Liting , Handler David C. L. , Multari Dylan , Haynes Paul A. 
Published: February 2020

ABSTRACTProteomics, as a high-throughput technology, has been developed with the aim of investigating the maximum number of proteins in cells. However, protein discovery and data generation vary in depth and coverage when different technical strategies are used. In this study, four different sample preparation, and peptide or protein fractionation, methods were applied to identify and quantify proteins from log-phase yeast lysate: sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE); gas phase fractionation (GPF); filter-aided sample preparation (FASP)- GPF; and FASP-high pH reversed phase fractionation (HpH). Fractionated samples were initially analyzed and compared using nanoflow liquid chromatography-tandem mass spectrometry (LC-MS/MS) employing data dependent acquisition on a linear ion trap instrument. The number of fractions and replicates was adjusted so that each experiment used a similar amount of mass spectrometric instrument time, approximately 16 hours. A second set of experiments was performed using a Q Exactive Orbitrap instrument, comparing FASP-GPF, SDS-PAGE and FASP-HpH. Compared with results from the linear ion trap mass spectrometer, the use of a Q Exactive Orbitrap mass spectrometer enabled a small increase in protein identifications using SDS-PAGE and FASP-GPF methods, and a large increase using FASP-HpH. A big advantage of using the higher resolution instrument found in this study was the substantially increased peptide identifications which enhance the proteome coverage. A total of 1035, 1357 and 2134 proteins were separately identified by FASP-GPF, SDS-PAGE and FASP-HpH. Combining results from the Orbitrap experiments, there were a total of 2269 proteins found, with 94% of them identified using the FASP-HpH method. Therefore, the FASP-HpH method is the optimal choice among these approaches when using a high resolution spectrometer, when applied to this type of sample.
In situstructural analysis of the flagellum attachment zone inTrypanosoma bruceiusing cryo-scanning transmission electron tomography
Authors: Trépout Sylvain 
Published: February 2020

SummaryThe flagellum ofTrypanosoma bruceiis a 20 µm-long organelle responsible for locomotion and cell morphogenesis. The flagellum attachment zone (FAZ) is a multi-protein complex whose function is to attach the flagellum to the cell body but also to guide cytokinesis. Cryo-transmission electron microscopy is a tool of choice to access the structure of the FAZ in a close-to-native state. However, because of the large dimension of the cell body, the whole FAZ cannot be structurally studiedin situat high resolution in 3D using classical transmission electron microscopy approaches. In the present work, cryo-scanning transmission electron tomography, a new method capable of investigating cryo-fixed thick biological samples, has been used to study wholeT. bruceicells at the bloodstream stage. The method has been used to visualise and characterise the structure and organisation of the FAZ filament. It is composed of an array of cytoplasmic stick-like structures. These sticks are heterogeneously distributed between the posterior part and the anterior tip of the cell. This cryo-STET investigation provides new insights in the structure the FAZ filament. In combination with protein structure predictions, this work proposes a new model for the elongation of the FAZ.HighlightsFlagellar and cellular membranes are in close contact next to the FAZ filamentSticks are heterogeneously distributed along the FAZ filament lengthThin appendages are present between the FAZ filament sticks to neighbouring microtubulesFAZ elongation could originate from the force exerted by dynein motors on subpellicular microtubules
Improved discrimination of asymmetric and symmetric arginine dimethylation by optimization of the normalized collision energy in LC-MS proteomics
Authors: Hartel Nicolas G. , Liu Christopher Z. , Graham Nicholas A. 
Published: February 2020

ABSTRACTProtein arginine methylation regulates diverse biological processes including signaling, metabolism, splicing, and transcription. Despite its important biological roles, arginine methylation remains an understudied post-translational modification. Partly, this is because the two forms of arginine dimethylation, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are isobaric and therefore indistinguishable by traditional mass spectrometry techniques. Thus, there exists a need for methods that can differentiate these two modifications. Recently, it has been shown that the ADMA and SDMA can be distinguished by the characteristic neutral loss (NL) of dimethylamine and methylamine, respectively. However, the utility of this method is limited because the vast majority of dimethylarginine peptides do not generate measurable NL ions. Here, we report that increasing the normalized collision energy (NCE) in a higher-energy collisional dissociation (HCD) cell increases the generation of the characteristic NL that distinguish ADMA and SDMA. By analyzing both synthetic and endogenous methyl-peptides, we identify an optimal NCE value that maximizes NL generation and simultaneously improves methyl-peptide identification. Using two orthogonal methyl peptide enrichment strategies, high pH strong cation exchange (SCX) and immunoaffinity purification (IAP), we demonstrate that the optimal NCE increases improves NL-based ADMA and SDMA annotation and methyl peptide identifications by 125% and 17%, respectively, compared to the standard NCE. This simple parameter change will greatly facilitate the identification and annotation of ADMA and SDMA in mass spectrometry-based methyl-proteomics to improve our understanding of how these modifications differentially regulate protein function.
Psychological contract violation and patient’s antisocial behaviour
Authors: Chang Po-Chien , Wu Ting , Du Juan 
Published: February 2020

PurposeThe purpose of this study is to examine the dual effects of the violation of psychological contract on patient’s antisocial behaviour via the mediator of patient trust and the role of doctor-patient communication as a critical contingent variable in the psychological contract violation of patient’s antisocial behaviour relationship.Design/methodology/approachThe data were collected from 483 hospitalized patients distributed in Shanxi province, China by using a self-administered survey.FindingsThe results indicated that psychological contract violation is positively associated with patient antisocial behaviour via patient trust. Moreover, the study found that doctor-patient communication moderates the mediated effects of psychological contract violation on patient’s antisocial behaviour through patient trust; that is, the mediated effect on antisocial behaviour is weaker when both doctor and patients have more communication.Research limitations/implicationsDue to a cross-sectional design in nature, the causal relationship cannot be developed based on the results. Despite the limitation, the present study provides insights for improving doctor-patient relationship by emphasizing the importance of increasing patient trust and doctor-patient communication.Practical implicationsTo improve the quality of doctor-patient relationship, this study addresses the significance of properly showing understandings and care to regain mutual trust and reducing the likelihood of patient’s antisocial behaviour.Social implicationsThe research findings have implications for both the health system and medical schools in China to reinforce the professional ethics and improve their medical humanities as the main concerns to generate a more sustainable doctor–patient relationship.Originality/valueThis study includes patient trust as a mediator and doctor-patient communication as a moderator to investigate the moderated mediation relationship among patients and medical professionals. By further examining the doctor-patient relationship, the results may not only help improve the efficient implementation of medical practices but also support the institutes and develop medical professionals for more positive doctor-patient relationships.
Cultural equity: knowledge and outcomes aspects
Authors: Torelli Carlos J. , Oh Hyewon , Stoner Jennifer L. 
Published: February 2020

PurposeThe purpose of this paper is to propose cultural equity as a construct to better understand the characteristics that define a culturally symbolic brand and the downstream consequences for consumer behavior and nation branding in the era of globalization.Design/methodology/approachThis paper is an empirical investigation of the knowledge and outcome aspects of cultural equity with a total of 1,771 consumers located in three different countries/continents, 77 different brands as stimuli, and using a variety of measures, surveys, lab experiments, procedures and consumer contexts.FindingsCultural equity is the facet of brand equity attributed to the brand's cultural symbolism or the favorable responses by consumers to the cultural symbolism of a brand. A brand has cultural equity if it has a distinctive cultural symbolism in consumers' minds (brand knowledge aspect of cultural equity: association with the central concept that defines the culture, embodiment of culturally relevant values and embeddedness in a cultural knowledge network), and such symbolism elicits a favorable consumer response to the marketing of the brand (outcome aspect of cultural equity: favorable evaluations and strong self-brand connections).Practical implicationsThis paper offers a framework that allows marketers to develop cultural positioning strategies in hyper-competitive and globalized markets and identify ways for building and protecting their brands' cultural equity.Originality/valueThis paper advances our understanding of brands as cultural symbols by introducing cultural equity and integrates prior research on brand equity, cross-cultural differences in consumer behavior, country-of-origin effects and nation branding.
Tracing the evolution of the literature on knowledge management in inter-organizational contexts: a bibliometric analysis
Authors: Agostini Lara , Nosella Anna , Sarala Riikka , Spender J.-C. , Wegner Douglas 
Published: February 2020

PurposeBased on the growing interest devoted to knowledge management (KM) in inter-organizational contexts, the purpose of this paper is to systematize existing literature and understand how it developed over time, thus tracing its roots and evolution to unveil gaps and suggest new promising areas for future research.Design/methodology/approachThis study used bibliographic techniques to analyze a sample of 85 studies along three main periods (1998-2010, 2011-2014 and 2015-2019). In particular, this study focused on co-occurrences of keywords to identify the most dominant themes, as well as connections among these themes.FindingsOverall, the review shows the main outlets that have published papers on the topic of KM in inter-organizational contexts, as well as the theoretical background this research builds on. The temporal analysis exhibits the core topics that have persisted and grown consistently over time as the links between KM, innovation and networks. In addition, the review highlights new emerging themes, such as the human and social side of KM, and new interesting contexts of study (e.g. coopetition and open/user innovation), which opens exciting avenues for new research opportunities.Originality/valueThis study illustrates the conceptual structure of the field in three distinct periods and contributes to a more nuanced understanding of the key topics and their interrelatedness within the area of KM in inter-organizational contexts. Both researchers and practitioners can profit from the study because it reveals consolidated topics while identifying areas that still need to be investigated to foster KM in inter-organizational settings.
Legal challenges and opportunities of blockchain technology in the real estate sector
Authors: Garcia-Teruel Rosa M. 
Published: February 2020

PurposeBlockchain, which was originally created to enable peer-to-peer digital payment systems (bitcoin), is considered to have several benefits for different sectors, such as the real estate one. In a standard European-wide real estate transaction, several intermediaries are involved. As a consequence, these agreements are usually time-consuming and involve extra difficulties to cross-border operations. As blockchain, combined with smart contracts, may have an important role in these transactions, this paper aims to explore its prospective challenges, limitations and opportunities in the real estate sector and discover how the traditional intermediaries have to face a possible implementation of this technology.Design/methodology/approachThis paper analyses the current intermediaries in the real estate sector in European Union (EU), their functions and how can blockchain strengthen the security of these transactions while reducing their time. The author uses a legal methodology to approach it.FindingsBlockchain, combined with smart contracts, has both challenges and opportunities for the real estate sector. On the one hand, it may improve procedures, allow EU transactions and the interconnection between public administration. However, to not reduce parties rights, this blockchain should have some special features, such as the possibility of being amended.Originality/valueThis paper provides a valuable overview of all the intermediaries that could be affected by blockchain protocols. It is of interest of blockchain developers, public administrations and researchers who are working on blockchain and property conveyancing.