bluuebunny/crossref_metadata_2025_split huggingface dataset:
MKP-1 modulates Ubiquitination/Phosphorylation of TLR signaling
Authors: Talreja Jaya , Bauerfeld Christian , Wang Xiantao , Hafner Markus , Liu Yusen , Samavati Lobelia 
Published: June 2021

AbstractUbiquitination and phosphorylation are reversible post-translational protein modifications regulating physiological and pathological processes. MAPK phosphatase (MKP)-1 regulates innate and adaptive immunity. The multifaceted roles of MKP-1 were attributed to dephosphorylation of p38 and JNK mitogen activated kinases (MAPKs). We show that the lack of MKP-1 modulates the landscape of ubiquitin ligases and deubiquitinase enzymes (DUBs). MKP-1 deficient mice showed an aberrant regulation of several DUBs and increased expression of proteins and genes involved in IL-1/TLR signaling upstream of MAPK, including IL-1R1, IRAK1, TRAF6, phosphorylated TAK1 and an increased K63-polyubiquitination on TRAF6. Increased K63-polyubiquitination on TRAF6 was associated with an enhanced phosphorylated form of A20. Among abundant DUBs, Ubiquitin-specific-protease-13 (USP13), which cleaves polyubiquitin- chains on client proteins, was substantially enhanced in murine MKP-1 deficient BMDMs. An inhibitor of USP13 decreased the K63-polyubiquitination on TRAF6, TAK1-phosphorylation, IL-1β and TNF-α induction in response to LPS in BMDMs. Our data show for the first time that MKP-1 modulates the ligase activity of TRAF6 through modulation of specific DUBs.
Sustained mechanical tension governs fibrogenic activation of tendon stromal cells in systemic sclerosis
Authors: Hussien Amro A. , Knell Robert , Renoux Florian , Wunderli Stefania L. , Niederoest Barbara , Foolen Jasper , Distler Oliver , Snedeker Jess G. 
Published: June 2021

AbstractFibrosis is a pathological outcome of aberrant repair responses in systemic sclerosis and affects many tissues, including tendons. Progressive matrix stiffening is a key feature of this pathological remodeling. How dysregulated tissue mechanics contribute to the persistence of the fibrotic phenotype has been obscured by limited availability of experimental tissue models that are both controllable and capture essential aspects of the tendon biophysical niche. Here, we developed a modular, cantilever-based platform that allows culture of 3D tendon-like constructs under easily variable static tension, emulating this central tendon-specific structure function relationship. The system reveals that elevated matrix tension instigates fibroblast-to-myofibroblast activation eliciting scar-like phenotypes in vitro. By using this mechano-culture system and preclinical and clinical models of systemic sclerosis, we further show that 3D matrix stiffness is inversely correlated with the transcription of major pro-fibrotic collagens, but positively correlate with the expression of markers of stromal-immune interactions. Co-culture of tendon stromal fibroblasts and bone marrow-derived macrophages override stiffness-mediated downregulation of matrix transcription, suggesting that normal tension mediated checkpoints are superseded by the local tissue immune state. Our study highlights the power of 3D reductionist approaches in dissecting the contribution of the elevated matrix tension to the positive feedforward loops between activated fibroblasts and progressive ECM stiffening in systemic sclerosis.
A high-quality functional genome assembly of Delia radicum L. (Diptera: Anthomiidae) annotated from egg to adult
Authors: Sontowski Rebekka , Poeschl Yvonne , Okamura Yu , Vogel Heiko , Guyomar Cervin , Cortesero Anne-Marie , van Dam Nicole M. 
Published: June 2021

AbstractBelowground herbivores are overseen and underestimated, even though they can cause significant economic losses in agriculture. The cabbage root fly Delia radicum (Anthomyiidae) is a common pest in Brassica species, including agriculturally important crops, such as oil seed rape. The damage is caused by the larvae, which feed specifically on the taproots of Brassica plants until they pupate. The adults are aboveground-living generalists feeding on pollen and nectar. Female flies are attracted by chemical cues in Brassica plants for oviposition. An assembled and annotated genome can elucidate which genetic mechanisms underlie the adaptation of D. radicum to its host plants and their specific chemical defenses, in particular isothiocyanates. Therefore, we assembled, annotated and analyzed the D. radicum genome using a combination of different Next Generation Sequencing and bioinformatic approaches. We assembled a chromosome-level D. radicum genome using PacBio and Hi-C Illumina sequence data. Combining Canu and 3D-DNA genome assembler, we constructed a 1.3 Gbp genome with an N50 of 242 Mbp and 6 pseudo-chromosomes. To annotate the assembled D. radicum genome, we combined homology-, transcriptome- and ab initio-prediction approaches. In total, we annotated 13,618 genes that were predicted by at least two approaches. We analyzed egg, larval, pupal and adult transcriptomes in relation to life-stage specific molecular functions. This high-quality annotated genome of D. radicum is a first step to understanding the genetic mechanisms underlying host plant adaptation. As such, it will be an important resource to find novel and sustainable approaches to reduce crop losses to these pests.
The asymmetric Pitx2 regulates intestinal muscular-lacteal development and protects against fatty liver disease
Authors: Hu Shing , Mahadevan Aparna , Elysee Isaac F. , Choi Joseph , Souchet Nathan R. , Bae Gloria H. , Taboada Alessandra K. , Duhamel Gerald E. , Sevier Carolyn S. , Tao Ge , Kurpios Natasza A. 
Published: June 2021

SUMMARYIntestinal lacteals are the essential lymphatic channels for absorption and transport of dietary lipids and drive pathogenesis of debilitating metabolic diseases. Yet, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover a novel intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer, ASE, alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic-dependent lipid transport. Surprisingly, activation of lymphatic-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. In summary, our studies reveal the molecular mechanism linking gut lymphatic development to the earliest symmetry-breaking Pitx2 and highlight the important relationship between intestinal lymphangiogenesis and gut-liver axis.
GRAPHICAL ABSTRACTHIGHLIGHTS∼ Gut lymphangiogenesis is linked to Pitx2-driven LR asymmetry∼ Lacteal-associated smooth muscle requires ASE∼ ASE deletion leads to redox imbalance in intestinal smooth muscle lineage∼ ASE is required for the normal route of dietary lipid transport∼ Pitx2ASE/ASE neonates develop diet-induced fatty liver disease
High-level language brain regions are sensitive to sub-lexical regularities
Authors: Regev Tamar I. , Affourtit Josef , Chen Xuanyi , Schipper Abigail E. , Bergen Leon , Mahowald Kyle , Fedorenko Evelina 
Published: June 2021

ABSTRACTA network of left frontal and temporal brain regions supports ‘high-level’ language processing— including the processing of word meanings, as well as word-combinatorial processing—across presentation modalities. This ‘core’ language network has been argued to store our knowledge of words and constructions as well as constraints on how those combine to form sentences. However, our linguistic knowledge additionally includes information about sounds (phonemes) and how they combine to form clusters, syllables, and words. Is this knowledge of phoneme combinatorics also represented in these language regions? Across five fMRI experiments, we investigated the sensitivity of high-level language processing brain regions to sub-lexical linguistic sound patterns by examining responses to diverse nonwords—sequences of sounds/letters that do not constitute real words (e.g., punes, silory, flope). We establish robust responses in the language network to visually (Experiment 1a, n=605) and auditorily (Experiments 1b, n=12, and 1c, n=13) presented nonwords relative to baseline. In Experiment 2 (n=16), we find stronger responses to nonwords that obey the phoneme-combinatorial constraints of English. Finally, in Experiment 3 (n=14) and a post-hoc analysis of Experiment 2, we provide suggestive evidence that the responses in Experiments 1 and 2 are not due to the activation of real words that share some phonology with the nonwords. The results suggest that knowledge of phoneme combinatorics and representations of sub-lexical linguistic sound patterns are stored within the same fronto-temporal network that stores higher-level linguistic knowledge and supports word and sentence comprehension.
Distinct neural dynamics underlie the encoding of visual speed in stationary and running mice
Authors: Horrocks Edward A B , Saleem Aman B 
Published: June 2021

AbstractSensory experiences are often driven by an animal’s self-motion and locomotion is known to modulate neural responses in the mouse visual system. This modulation is hypothesised to improve the processing of behaviourally relevant visual inputs, which may change rapidly during locomotion. However, little is known about how locomotion modulates the temporal dynamics (time courses) of visually-evoked neural responses. Here, we analysed the temporal dynamics of single neuron and population responses to dot field stimuli moving at a range of visual speeds using the Visual Coding dataset from the Allen Institute for Brain Science1. Single neuron responses had diverse temporal dynamics that varied between stationary and running sessions. Increased dynamic range and more reliable responses in running sessions enabled faster, stronger and more persistent encoding of visual speed. Population activity reflected the temporal dynamics of single neuron responses, including their modulation by locomotor state - neural trajectories of population activity made more direct transitions between baseline and stimulus steady states in running sessions. The structure of population coding also changed with locomotor state – population activity prioritised the encoding of visual speed in running, but not stationary sessions. Our results reveal a profound influence of locomotion on the temporal dynamics of neural responses. We demonstrate that during locomotion, mouse visual areas prioritise the encoding of potentially fast-changing, behaviourally relevant visual features.
The role of hub neurons in modulating cortical dynamics
Authors: Gal Eyal , Amsalem Oren , Schindel Alon , London Michael , Schürmann Felix , Markram Henry , Segev Idan 
Published: June 2021

AbstractMany neurodegenerative diseases are associated with the death of specific neuron types in particular brain regions. What makes the death of specific neuron types particularly harmful for the integrity and dynamics of the respective network is not well understood. To start addressing this question we used the most up-to-date biologically-realistic dense neocortical microcircuit (NMC) of rodent, which has reconstructed a volume of 0.3 mm3 and containing 31,000 neurons, 36 million synapses, and 55 morphological cell types arranged in 6 cortical layers. Using modern network science tools, we identified “hub-neurons” in the NMC, that are connected synaptically to a large number of their neighbors and systematically examined the impact of abolishing these cells. In general, the structural integrity of the network is robust to cells’ attack; yet, attacking hub neurons strongly impacted the “small worldness” topology of the network, whereas similar attacks on random neurons have a negligible effect. Such hub-specific attacks are also impactful on the network dynamics, both when the network is at its spontaneous synchronous state and when it was presented with synchronized thalamo-cortical visual-like input. We found that attacking layer 5 hub neurons are most harmful to the structural and functional integrity of the NMC. The significance of our results for understanding the role of specific neuron types and cortical layers for disease manifestation is discussed.
Supply chain dynamics, big data capability and product performance
Authors: Lin Canchu , Kunnathur Anand , Forrest Jeffrey 
Published: June 2021

PurposeThe purpose of this study is to examine big data capability's impact on product improvement and explore supply chain dynamics including relationship building and knowledge sharing as important contribution to big data capability.Design/methodology/approachThe research model is tested with survey data. Data analysis results empirically support the proposed model and the hypothesized relationships between the concepts.FindingsFirst, the hypothesis testing results of this study show that big data capability directly enhances product improvement. Second, this study shows that supply chain relationship building and knowledge sharing are positively related to the development of big data capability.Research limitations/implicationsIn supply chain management, there are multiple factors, besides relationship building, that serve as conditioners to knowledge sharing's effect on product performance. We only examined the role of relationship building in this area.Practical implicationsFindings from this research encourage firms to take advantage of their supply chain resources to develop a big data capability that positively contributes to firm performance.Originality/valueThe contribution lies in that it brings to light this step that connects big data capabilities and market and financial performance, which is missing in prior research. This study contributes to the literature by identifying supply chain management activities, more specifically, supply chain relationship building and knowledge sharing, as antecedents to big data capability. This helps to extend this emergent enterprise of big data research to a new area and points to new directions for future research.
The meso-failure mechanism of lightweight concrete simulated by the phase field method
Authors: Wang Jichang , Guo Xiaoming 
Published: June 2021

PurposeA mesoscopic phase field (PF) model is proposed to simulate the meso-failure process of lightweight concrete.Design/methodology/approachThe PF damage model is applied to the meso-failure process of lightweight concrete through the ABAQUS subroutine user-defined element (UEL). And the improved staggered iteration scheme with a one-pass procedure is used to alternately solve the coupling equations.FindingsThese examples clearly show that the crack initiation of the lightweight concrete specimens mainly occurs in the ceramsite aggregates with weak strength, especially in the larger aggregates. The crack propagation paths of the specimens with the same volume fraction of light aggregates are completely different, but the crack propagation paths all pass through the ceramsite aggregates near the cracks. The results also showed that with the increase in the volume fractions of the aggregates, the slope and the peak loads of the force-deflection (F-d) curves gradually decrease, the load-bearing capacity of the lightweight concrete specimens decreases, and crack branching and coalescence are less likely during crack propagation.Originality/valueThe mesostructures with a mortar matrix, aggregates and an interfacial transition zone (ITZ) are generated by an automatic generation and placement program, thus incorporating the typical three-phase characteristics of lightweight concrete into the PF model.
Moving beyond the rhetoric on faculty diversity in higher education: an interview with diversity expert Dr Bailey Jackson
Authors: Gavino Monica C. 
Published: June 2021

PurposeThe aim of this article is to provide Dr Bailey Jackson's perspective on institutional and systemic barriers to full inclusion of diverse faculty in higher education through the lens of the multicultural organizational development (MCOD) model. Dr Jackson is renowned for his work on social justice, diversity and multiculturalism.Design/methodology/approachThis is a personal interview with Dr Bailey Jackson. This interview provides insight on institutional level change efforts through the MCOD framework, a perspective on why institutions get stuck on the way to becoming healthy multicultural institutions, and the effect on moving the needle on faculty diversity in institutions of higher education.FindingsThe institutional obstacles and barriers tend to be centered around misalignment with the mission, vision and core values, and how those are formulated to include diversity and inclusion. Faculty diversity is only one component in dealing with the health of any organization or the academy as a whole. If institutions focus on diversity faculty in an unhealthy system, they will encounter limitations on how much the institution will develop on the MCOD continuum. The health of the overall system is going to affect the approach to faculty diversity.Practical implicationsDr Jackson provides insight on his work with the MCOD framework and specifically the overall health of the institution as critical to faculty diversity initiatives. Questions to help institutions begin to assess themselves and identify changes required to move toward Multicultural within the context of faculty diversity are provided.Originality/valueThrough a series of questions, insight from Dr Jackson on why institutions get stuck in moving the needle on faculty diversity through the lens of the MCOD framework is gained.
A synthetic indicator of market leaders in the crowdlending sector
Authors: Ribeiro-Navarrete Samuel , Palacios-Marqués Daniel , Martín Martín José María , Guaita Martínez José Manuel 
Published: June 2021

PurposeThis study contributes to the limited literature on crowdlending by providing a data-driven analysis of the sector. A synthetic DP2 indicator is proposed to identify the leaders of the crowdlending market, the key factors behind their success and the medium-term competitive implications.Design/methodology/approachThe study examines 17 crowdlending platforms and eight performance indicators. The information provided by these indicators is aggregated using a synthetic indicator based on theP2Distance (DP2) method.FindingsMintos, Evoestate, Peerberry, Bondster and Fellow Finance are the leading platforms. This method reveals the key variables in the identification of market leaders, namely year-on-year variation in the number of investors and year-on-year variation in lending per investor. The leaders in terms of lending volumes should not take their current situation for granted. Small and medium-sized platforms are pushing hard and may overtake the incumbents as market leaders.Practical implicationsFinancial intermediation through crowdlending is becoming an increasingly popular alternative to traditional models. Changes in the sector are expected in the coming years due to the rise of platforms with a moderate amount of lending and solid year-on-year improvement. To become leaders and to attract both lenders and borrowers, platforms are encouraged to improve the information that they provide.Originality/valueThis paper offers the first analysis of market leadership in the crowdlending sector. It analyses the competitive market of the crowdlending sector based on its actors and key factors. These factors explain the differences in the market position of different platforms. Based on this analysis, the trends in this sector can be identified. This study is exploratory, so it offers empirical data that can be useful in the development of theories that apply to the sector.
Pharmacy service factors and pharmacy performance: the role of patient satisfaction in community pharmacies
Authors: Barghouth Dana , Al-Abdallah Ghaith M. , Abdallah Ayman Bahjat 
Published: June 2021

Purpose
This study aims to examine the effects of pharmacy service factors (namely, medication teaching, service promptness, pharmacist attitudes, medication supply and pharmacy location) on patient satisfaction with community pharmacies in Jordan and to explore the effect of patient satisfaction on pharmacy performance.

Design/methodology/approach
Descriptive analytical methodology, with a quantitative approach using survey strategy was applied. The study population represented the whole population of Jordan (2.033 million households). Data were collected using an online questionnaire. A convenient quota sample of 1,000 respondents was targeted; 502 valid questionnaires were returned, representing an effective response rate of 50.2%. The study hypotheses were tested using path analysis.

Findings
The results showed that the service factors contributing most significantly to patient satisfaction in Jordan are medication supply, pharmacist attitudes, medication teaching and service promptness, in descending order of influence. Meanwhile, the effect of pharmacy location on patient satisfaction proved to be insignificant. In addition, patient satisfaction proved to have a highly positive impact on pharmacy performance.

Originality/value
This study addresses a debatable issue in the literature regarding the influence that pharmacy service factors can have on patient satisfaction. In addition, to the best of the researchers’ knowledge, this is the first study to explore the proposed effects in Jordan. It is also one of the first to investigate the effect of patient satisfaction on community pharmacy performance.
Performance evaluation in humanitarian operations based on the beneficiary perspective
Authors: Cardoso Brenda , Fontainha Tharcisio , Leiras Adriana , Cardoso Patricia Alcantara 
Published: June 2021

PurposeThis paper aims to identify the main performance criteria for Humanitarian Operations (HOs) from the beneficiary perspective and to propose a taxonomy to support the evaluation of stakeholders.Design/methodology/approachThe research conducts a Systematic Literature Review to identify the main criteria in HOs from the beneficiary's view. Also, we conduct an empirical study based on a survey and a case study to validate the findings in a real-life setting.FindingsConsidering 25 papers, the identified performance criteria were divided into six categories: health, housing, education, socioeconomic factors, care and risk and disaster management. The empirical discussion considered forty-four responses from beneficiaries, and the main criteria complained about were related to socioeconomic factors. In addition, a case study was developed that examines the perspective of the company responsible for the construction of the building to aid in understanding the areas of dissatisfaction noted by the residents.Practical implicationsThe research contributes organized criteria to support the performance evaluation of organizations. It offers a structured basis for further discussion among academics and professionals about other performance evaluation topics, such as dashboards and the integration of indicators from different stakeholders.Originality/valueLiterature is scarce in questions of performance evaluation in HOs and the analysis of the beneficiary as the main client. Therefore, the paper contributes to both areas by evaluating HOs from the beneficiary's perspective.