bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteome Remodeling of the Eye Lens at 50 Years Identified with Data-Independent Acquisition
Authors: Cantrell Lee S. , Schey Kevin L. 
Published: May 2022

AbstractThe eye lens is responsible for focusing and transmitting light to the retina. The lens does this in the absence of organelles yet maintains transparency for at least five decades before onset of age-related nuclear cataract (ARNC). It is hypothesized that oxidative stress contributes significantly to ARNC formation. It is additionally hypothesized that transparency is maintained by a microcirculation system (MCS) that delivers antioxidants to the lens nucleus and exports small molecule waste. Common data-ependent acquisition (DDA) methods are hindered by dynamic range of lens protein expression and provide limited context to age-related changes in the lens. In this study we utilized data-independent acquisition (DIA) mass spectrometry to analyze the urea insoluble, membrane protein fractions of 16 human lenses subdivided into three spatially distinct lens regions to characterize age-related changes, particularly concerning the lens MCS and oxidative stress response. In this pilot cohort, we measured 4,788 distinct protein groups, 46,681 peptides, and 7,592 deamidated sequences, more than in any previous human lens DDA approach. Our results reveal age-related changes previously known in lens biology and expand on these findings, taking advantage of the rich dataset afforded by DIA. Principally, we demonstrate that a significant proteome remodeling event occurs at approximately 50 years of age, resulting in metabolic preference for anaerobic glycolysis established with organelle degradation, decreased abundance of protein networks involved in calcium-dependent cell-cell contacts while retaining networks related to oxidative stress response. Further, we identified multiple antioxidant transporter proteins not previously detected in the human lens and describe their spatiotemporal and age-related abundance changes. Finally, we demonstrate that aquaporin-5, among other proteins, is modified with age by PTMs including deamidation and truncation. We suggest that the continued accumulation of each of these age-related outcomes in proteome remodeling contribute to decreased fiber cell permeability and result in ARNC formation.
Modulation of Tau Tubulin Kinases (TTBK1 and TTBK2) Impacts Ciliogenesis
Authors: Potjewyd Frances M. , Marquez Ariana B. , Chaikuad Apirat , Howell Stefanie , Dunn Andrea S. , Beltran Alvaro A. , Smith Jeffery L. , Drewry David H. , Beltran Adriana S. , Axtman Alison D. 
Published: May 2022

SUMMARYTau tubulin kinase 1 and 2 (TTBK1 and TTBK2) are highly homologous kinases that are expressed and mediate disease-relevant pathways predominantly in the brain. Distinct roles for TTBK1 and TTBK2 have been delineated. While efforts have been devoted to characterizing the impact to TTBK1 inhibition in diseases like Alzheimer’s disease and amyotrophic lateral sclerosis, TTBK2 inhibition has been less explored. TTBK2 serves a critical function during cilia assembly. Given the biological importance of these kinases, we designed a targeted library from which we identified several chemical tools that engage TTBK1 and TTBK2 in cells and inhibit their downstream signaling. Indolyl pyrimidinamine 10 significantly reduced the expression of primary cilia on the surface of human induced pluripotent stem cells (iPSCs). Furthermore, analog 10 phenocopies TTBK2 KO in iPSCs, confirming an essential role for TTBK2 in ciliogenesis.
Single-cell atlas of mouse limb development reveals a complex spatiotemporal dynamics of skeleton formation
Authors: Markman Svetlana , Zada Mor , David Eyal , Giladi Amir , Amit Ido , Zelzer Elazar 
Published: May 2022

AbstractLimb development has long served as a model system for coordinated spatial patterning of progenitor cells. Here, we identify a population of naïve limb progenitors and show that they differentiate progressively to form the skeleton in a complex nonconsecutive three-dimensional pattern.Single-cell RNA sequencing of the developing mouse forelimb revealed three progenitor states: naïve, proximal and autopodial, as well as Msx1 as a marker for the naïve progenitors. In vivo lineage tracing confirmed this role and localized the naïve progenitors to the outer margin of the limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that the progressive transition of Msx1+ naïve progenitors into proximal and autopodial progenitors coincides with their differentiation to Sox9+ chondroprogenitors, which occurs along all the forming skeletal segments.Indeed, tracking the spatiotemporal sequence of differentiation showed that the skeleton forms progressively in a complex pattern. These findings suggest a new model for limb skeleton development.
Analysis of front end dynamic in the value co-creation with multiple stakeholders
Authors: Takahashi Sérgio , Takahashi Vania Passarini 
Published: May 2022

PurposeThis study aims to analyze the dynamic of front end development (discover, define and create/analysis and test phases) in the co-creation with multiple stakeholders taking into account the value creation and capture process in a strategic business, consulting project, adding knowledge sharing flows.Design/methodology/approachThe first phase of the study consisted of a review of the narrative literature. The method chosen for analyzing the findings is the narrative synthesis, which sought to identify and show the complementarity between the areas studied. Then, a summary of the review presents a conceptual structure. At the third phase of the study consisted of a field survey characterized for being a descriptive-exploratory and qualitative investigation based on a single case study.FindingsFor the results, three phases of evolution in the relationships among stakeholders can be characterized, namely: formation, strengthening and integration. With regard to value capture, it is also possible to characterize three phases of simultaneous non-linear evolution: sharing of perceptions, ideas and experiences, self-reflection, and vision and solution. With regard to knowledge sharing, two important flows were characterized: solution development and socialization and communication, in which there is a greater relationship with the development of trust, commitment, tie strengthening and shared vision. And some insights from the perspective of integrating dynamic capabilities and front end with value co-creation with multiple stakeholders.Originality/valuePractical and theorical results of the evolution of value co-creation on the front end phases dynamic.
The effect of R&D activities on the market response and company's performance during the shock caused by the COVID-19 pandemic in Iran
Authors: Behbahaninia Parisa Saadat , Golbidi Mohadeseh 
Published: May 2022

PurposeThe purpose of this study is to investigate whether research and development (R&D) activities reduce the performance damage caused by a critical situation, such as the COVID-19 pandemic, or not. Also, this study tries to explain whether the market in its reactions pays attention to companies' R&D activities or not during the COVID-19 critical situation.Design/methodology/approachThe official announcement of the COVID-19 disease in Iran is considered the date of the event in this study. To consider the effect of R&D activities on the performance, three similar time periods before and after the coronavirus pandemic have been considered. Due to the widespread prevalence of coronavirus in Iran, this country has been selected to answer the research questions.FindingsThe results showed that the companies that have more R&D activities performed better than other companies during this period and were able to better manage this crisis. Furthermore, companies with more R&D activities suffered lower abnormal returns during coronavirus shocks than other companies.Research limitations/implicationsBased on the research results, the issues that were discussed on the importance of R&D activities in the accounting literature is confirmed, and the results show the importance of R&D activities on the company's ability to overcome crises.Practical implicationsBased on the results of this research, it can be suggested that even in difficult and critical conditions, investment in R&D activities should not be stopped and decrease.Originality/valueIn the accounting literature, the long-term effect of R&D activities on the survival of companies has always been considered. In this study, the effect of R&D activities on market response and firm performance in a real shock is investigated, which is the innovation of this research.
A grey-based framework for circular supply chain management: a forward step towards sustainability
Authors: Khan Shahbaz , Haleem Abid , Khan Mohd Imran 
Published: May 2022

PurposeCircular supply chain management (CSCM) has the potential to compensate for the drawbacks of the linear supply chain model. Therefore, the objective of this study is to identify and prioritise the significant enablers related to the effective management of the circular supply chain (CSC).Design/methodology/approachThe significant enablers of CSCM are identified through a two-step process of literature review and grey-Delphi approach. Further, an integrated grey-based Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) is applied to prioritise these enablers.FindingsThis study proposes a grey-based framework to identify and evaluate the enablers associated with CSCM. A total of 12 significant CSCM enablers are finalised per the proposed framework. The findings suggest that the top three enablers are "long-term planning", "development of CE culture" and "alignment of CE goals with strategic objectives". These enablers require the attention of the top management and supply chain partner on priority.Research limitations/implicationsThis study identifies 12 enablers through the literature review, so there is a possibility to overlook some significant enablers. However, the expert's input is used to finalise and analyse the enablers, which can be biased towards their working level.Originality/valueThis study proposes a grey-based framework to identify and analyse the CSC enablers rarely investigated in the contemporary literature. The paper is strong in methodological contributions and gives practitioners and researchers a better framework for CSCM.
The influence of abusive supervision on employee engagement, stress and turnover intention
Authors: Oliveira Lucia B. , Najnudel Priscila Sarmento 
Published: May 2022

PurposeThe purpose of this research was to investigate the influence of abusive supervision on work engagement, stress and turnover intention of subordinates. It was also proposed that work engagement and stress mediate the relationship between abusive supervision and turnover intention. Self-determination theory and the job demands-resources (JD-R) model provide the theoretical framework for the hypotheses.Design/methodology/approachThe sample of this study consisted of 172 employees from public and private companies operating in different sectors of the economy. The hypotheses were tested through multiple regression analysis.FindingsThe results show that abusive supervision negatively influences engagement and contributes to increasing subordinates' stress and turnover intention. The study also found that the relationship between abusive supervision and turnover intention is mediated by engagement, but not by stress.Research limitations/implicationsData was obtained from a convenience sample and cannot, therefore, be generalized.Practical implicationsThe study results suggest that employees are prone to leave an organization when they are subordinated to abusive leaders, corroborating the idea that workers choose organizations but leave their leaders. This, in turn, reinforces the importance of adopting proper leadership selection and training processes.Originality/valueThis research addresses the dark side of the relationship between superiors and subordinates, which has been scarcely examined in the Brazilian literature. It also draws attention to different harmful consequences associated with dysfunctional behaviors of professionals that hold leadership positions in organizations.
Effect of Shadow Banking Activities on Firm Risk and Performance: Entrusted Loan Evidence from Chinese Listed Firms*
Authors: Wang Xiaoyan , Qiao Sijia , Shen Chung‐Hua , Wu Meng‐Wen , Wang Juan 
Published: May 2022

AbstractThis study investigates the effect of non‐financial firms' activities in shadow banking on firm risk and performance. Using manually collected data of entrusted loans from Chinese listed firms, we find that lending firms' bankruptcy risk and performance increases from their engagement of entrusted loan businesses in the year the loans are issued and in the following year. Further, firms' risk increases and performance improves significantly when firms are financially healthy, financially constrained, and non‐state‐owned. Overall, our findings provide policy implications that the risk of shadow banking activities must be cautious.
Exploring the role of Northeast Atlantic cod in the Barents Sea food web using a multi‐model approach
Authors: Nilsen Ina , Hansen Cecilie , Kaplan Isaac , Holmes Elizabeth , Langangen Øystein 
Published: May 2022

AbstractIt is commonly accepted that no ecosystem model is the ‘best’, but rather that ecosystem models should be used in ensembles. This is also the case for the Barents Sea ecosystem, where we have used two different ecosystem models to explore the role of the top‐predator Northeast Arctic (NEA) stock of Atlantic cod (Gadus morhua, Gadidae) in the food web. The two models differ in complexity; Gompertz being less complex in terms of food web (7 components) and processes compared to the complex Nordic and Barents Seas Atlantis model (53 components). On the other hand, Gompertz provides thousands of stochastic realizations for each scenario, whereas Atlantis provides only one deterministic simulation. To compare the response to changes in NEA cod on two key prey species, capelin (Mallotus villosus, Osmeridae) and polar cod (Boreogadus saida, Gadidae), we perturbed the historical fishing pressure by ±50% and used the same NEA cod biomass in both models. Even though the links between NEA cod and the prey species are similar in the two models, the results from the study reveal that indirect effects through other food‐web components might be as important as direct predator–prey interactions. Differences in spatial structure and overlap between species also influence the species response to the perturbations. In this study, we focus on the mechanisms that drives the changes in the models, and advise on potential consequences for fisheries management. The two models can complement each other, and the differences between them point to areas where more knowledge is needed.
Improved survival of cirrhotic patients with infections in Australian and New Zealand ICUs between 2005 and 2017
Authors: Majeed Ammar , Bailey Michael , Kemp William , Majumdar Avik , Bellomo Rinaldo , Pilcher David , Roberts Stuart K. 
Published: May 2022

AbstractBackground & AimsChanges in outcomes of cirrhotic patients admitted to intensive care units (ICUs) with infections are poorly understood. We aimed to describe changes over time in outcomes for such patients and to compare them to other ICU admissions.MethodsAnalysis of consecutive admissions to 188 ICUs between 2005 and 2017 as recorded in the Australian and New Zealand Intensive Care Society Centre for Outcome and Research Evaluation Adult Patient Database.ResultsAdmissions for cirrhotic patients with infections accounted for 4645 (0.6%) of 813 189 non‐elective ICU admissions. Hospital mortality rate (35.5%) was significantly higher compared with other cirrhotic patients' admissions (28.5%), and other ICU admissions for infection (17.1%, p < .0001), and increased to 52.2% in the presence of acute‐on‐chronic liver failure (ACLF). Hospital mortality in cirrhotic patients' ICU admissions for infection decreased significantly over time (annual decline odds ratio, 0.97; 95% CI, 0.95–0.99, p = .002). There was a comparable reduction in‐hospital mortality rates over time in other ICU admissions for infections and other cirrhotic patients' ICU admissions. However, mortality rates did not change over time in the ACLF subgroup. Median hospital and ICU length of stays for cirrhotic patients' ICU admissions for infections were 12.1 and 3.5 days, respectively, and decreased significantly by 1 day every 4 years in‐hospital survivors(p < .0001).ConclusionHospital mortality in ICU admissions for cirrhotic patients with infection is double that of non‐cirrhotic patients with infection but has declined significantly over time. Outcomes in the subgroup with ACLF remained poor without significant improvement over the study period.
Odorant receptor orthologues in conifer‐feeding beetles display conserved responses to ecologically relevant odours
Authors: Roberts Rebecca E. , Biswas Twinkle , Yuvaraj Jothi Kumar , Grosse‐Wilde Ewald , Powell Daniel , Hansson Bill S. , Löfstedt Christer , Andersson Martin N. 
Published: May 2022

AbstractInsects are able to detect a plethora of olfactory cues using a divergent family of odorant receptors (ORs). Despite the divergent nature of this family, related species frequently express several evolutionarily conserved OR orthologues. In the largest order of insects, Coleoptera, it remains unknown whether OR orthologues have conserved or divergent functions in different species. Using HEK293 cells, we addressed this question through functional characterization of two groups of OR orthologues in three species of the Curculionidae (weevil) family, the conifer‐feeding bark beetles Ips typographus L. (“Ityp”) and Dendroctonus ponderosae Hopkins (“Dpon”) (Scolytinae), and the pine weevil Hylobius abietis L. (“Habi”; Molytinae). The ORs of H. abietis were annotated from antennal transcriptomes. The results show highly conserved response specificities, with one group of orthologues (HabiOR3/DponOR8/ItypOR6) responding exclusively to 2‐phenylethanol (2‐PE), and the other group (HabiOR4/DponOR9/ItypOR5) responding to angiosperm green leaf volatiles (GLVs). Both groups of orthologues belong to the coleopteran OR subfamily 2B, and share a common ancestor with OR5 in the cerambycid Megacyllene caryae, also tuned to 2‐PE, suggesting a shared evolutionary history of 2‐PE receptors across two beetle superfamilies. The detected compounds are ecologically relevant for conifer‐feeding curculionids, and are probably linked to fitness, with GLVs being used to avoid angiosperm nonhost plants, and 2‐PE being important for intraspecific communication and/or playing a putative role in beetle–microbe symbioses. To our knowledge, this study is the first to reveal evolutionary conservation of OR functions across several beetle species and hence sheds new light on the functional evolution of insect ORs.
Brain somatic mutations as RNA therapeutic targets in neurological disorders
Authors: Lee Sungyul , Lee Jeong Ho 
Published: May 2022

AbstractResearch into the genetic etiology of a neurological disorder can provide directions for genetic diagnosis and targeted therapy. In the past, germline mutations, which are transmitted from parents or newly arise from parental germ cells, were considered as major genetic causes of neurological disorders. However, recent evidence has shown that somatic mutations in the brain, which can arise from neural stem cells during development or over aging, account for a significant number of brain disorders, ranging from neurodevelopmental, neurodegenerative, and neuropsychiatric to neoplastic disease. Moreover, the identification of disease‐causing somatic mutations or mutated genes has provided new insights into molecular pathogenesis and unveiled potential therapeutic targets for treating neurological disorders that have few, or no, therapeutic options. RNA therapeutics, including antisense oligonucleotide (ASO) and small interfering RNA (siRNA), are emerging as promising therapeutic tools for treating genetic neurological disorders. As the number of approved and investigational ASO and siRNA drugs for neurological disorders associated with germline mutations increases, they may also prove to be attractive modalities for treating neurologic disorders resulting from somatic mutations. In this perspective, we highlight several neurological diseases caused by brain somatic mutations and discuss the potential role of RNA therapeutics in these conditions.
Complementarity of additionalities resulting from European Union funds: Perspective of the users of research infrastructures
Authors: Hegerty Scott W. , Kowalski Arkadiusz M. , Lewandowska Małgorzata S. 
Published: May 2022

AbstractThe goal of this paper is to investigate the complementarity of three types of additionalities: input (growth of R&D investments), behavioral (changes in the internal processes of the entity), and output (leveraging social or private returns), occurring as the result of the 7th Framework Programme and Horizon 2020 European Union funds part INFRA. The empirical contribution is based on results of self‐created questionnaires conducted in 2016 with the use of CATI/CAWI on the unique sample of N = 401 users of European Union research infrastructures from 32 countries. We create a Behavioral Additionality Index (BAI), which is a measurement tool that combines eight types (scale, scope, cognitive capacity, challenge, network, follow‐up, management, and acceleration) of behavioral additionalities. Based on the results of a logistic regression, we find that there is a positive relationship between input and behavioral additionality, as well as between behavioral additionality and output additionality. This last link, however, is not shown to be strengthened by input additionality. No significant differences in the level of the BAI were found between EU countries based on their level of innovativeness as measured by the Summary Innovation Index (SII), although we can observe that less developed EU countries, as well as on non‐EU countries, have higher BAI scores compared to developed ones. The overall results lead to the conclusion that the evaluation of public financial support has to be conducted not only for input, behavioral, and output additionalities separately, but must also take into account their complementarity—with its major focus on the behavioral aspects of this effect.