bluuebunny/crossref_metadata_2025_split huggingface dataset:
FAM114A1 Influences Cardiac Fibrosis by Regulating Angiotensin II Signaling in Cardiac Fibroblasts
Authors: Subbaiah Kadiam C Venkata , Wu Jiangbin , Tang Wai Hong Wilson , Yao Peng 
Published: February 2021

AbstractCardiac fibrosis, a primary contributor to heart failure (HF) and sudden death, is considered as an important target for HF therapy. However, the signaling pathways that govern cardiac fibroblast (CF) function during cardiac fibrosis have not been fully elucidated. Here, we found that a functionally unannotated human myocardial infarction (MI) associated gene, family with sequence similarity 114 member A1 (FAM114A1), is induced in failing human and mouse hearts compared to non-failing hearts. Homozygous knockout ofFam114a1(Fam114a1−/−) in the mouse genome reduces cardiac hypertrophy and fibrosis while significantly restores cardiac function in angiotensin (Ang) II- and MI-induced HF mouse models.Fam114a1deletion antagonizes Ang II induced inflammation and oxidative stress. Using isolated mouse primary CFs in wild type andFam114a1−/−mice, we found that FAM114A1 is a critical autonomous factor for CF proliferation, activation, and migration. We discovered that FAM114A1 interacts with angiotensin receptor associated protein (AGTRAP) and regulates the expression of angiotensin type 1 receptor (AT1R) and downstream Ang II signaling transduction, and subsequently influences pro-fibrotic response. Using RNA-Seq in mouse primary CFs, we identified differentially expressed genes including extracellular matrix proteins such as Adamts15. RNAi-mediated inactivation of Adamts15 attenuates CF activation and collagen deposition. Our results indicate that FAM114A1 regulates Ang II signaling and downstream pro-fibrotic and pro-inflammatory gene expression, thereby activating cardiac fibroblasts and augmenting pathological cardiac remodeling. These findings provide novel insights into regulation of cardiac fibrosis and identify FAM114A1 as a new therapeutic target for treatment of cardiac disease.SignificanceCardiac fibrosis is a hallmark of heart failure and angiotensin II signaling promotes pro-fibrotic response in the heart. This study is a pioneering investigation of the role of a functionally unknown protein FAM114A1. We show that FAM114A1 expression is induced in human and mouse failing hearts. Genetic ablation of FAM114A1 can effectively reduce cardiac fibrosis and pathological remodeling. Isolated cardiac fibroblasts fromFam114a1knockout mice show reduced response to Ang II stimulation and compromised myofibroblast activation. Mechanistically, FAM114A1 binds to AGTRAP and influences AT1R protein expression, thereby enhancing angiotensin II signaling and pro-fibrotic response. Thus, FAM114A1 is a novel factor that modulates cardiac fibrosis and pharmacological inhibition of FAM114A1 may be a therapeutic strategy for the treatment of heart disease.
Precise topology of adjacent domain-general and sensory-biased regions in the human brain
Authors: Assem Moataz , Shashidhara Sneha , Glasser Matthew F. , Duncan John 
Published: February 2021

AbstractRecent functional MRI studies identified sensory-biased regions across much of the association cortices and cerebellum. However, their anatomical relationship to multiple-demand (MD) regions, characterized as domain-general due to their co-activation during multiple cognitive demands, remains unclear. For a better anatomical delineation, we used multimodal MRI techniques of the Human Connectome Project to scan subjects performing visual and auditory versions of a working memory (WM) task. The contrast between hard and easy WM showed strong domain generality, with essentially identical patterns of cortical, subcortical and cerebellar MD activity for visual and auditory materials. In contrast, modality preferences were shown by contrasting easy WM with baseline; most MD regions showed visual preference while immediately adjacent to cortical MD regions, there were interleaved regions of both visual and auditory preference. The results may exemplify a general motif whereby domain-specific regions feed information into and out of an adjacent, integrative MD core.
A Transient Metabolic State In Melanoma Persister Cells Mediated By Chemotherapeutic Treatments
Authors: Karki Prashant , Angardi Vahideh , Mier Juan C. , Orman Mehmet A. 
Published: February 2021

ABSTRACTPersister cells are defined as the small fraction of quiescent cells in a bulk cancer cell population that can tolerate unusually high levels of drugs. Persistence is a transient state that poses an important health concern in cancer therapy. The mechanisms associated with persister phenotypes are highly diverse and complex, and many aspects of persister cell physiology remain to be explored. We applied a melanoma cell line and panel of chemotherapeutic agents to show that melanoma persister cells are not necessarily preexisting dormant cells or stem cells; in fact, they may be induced by cancer chemotherapeutics. Our metabolomics analysis and phenotype microarray assays further demonstrated that the levels of Krebs cycle molecules are significantly lower in the melanoma persister subpopulation than in the untreated bulk cell population due to increased utilization rates in persisters. Our data indicate that this observed metabolic remodeling is transient, as the consumption rates of Krebs cycle metabolites are significantly reduced in the progenies of persisters. Given that the mitochondrial electron transport chain (ETC) is more active in the persister subpopulation than in the bulk cancer cell population, we also verified that targeting ETC activity can reduce melanoma persistence. The reported metabolic remodeling feature seems to be a conserved characteristic of melanoma persistence, as it has been observed in various melanoma persister subpopulations derived from a diverse range of chemotherapeutics. Elucidating a global metabolic mechanism that contributes to persister survival and reversible switching will ultimately foster the development of novel cancer therapeutic strategies.
A chimeric nuclease substitutes CRISPR-Cas: A phage weaponizes laterally acquired specificity to destroy subviral parasites
Authors: Barth Zachary K. , Nguyen Maria H.T. , Seed Kimberley D. 
Published: February 2021

AbstractMobile genetic elements, elements that can move horizontally between genomes, have profound effects on their hosts fitness. The PLE is a mobile element that integrates into the chromosome ofVibrio choleraeand parasitizes the bacteriophage ICP1 to move between cells. This parasitism by PLE is such that it abolishes the production of ICP1 progeny and provides a defensive boon to the host cell population. In response to the severe parasitism imposed by PLE, ICP1 has acquired an adaptive CRISPR-Cas system that targets the PLE genome during infection. However, ICP1 isolates that naturally lack CRISPR-Cas are still able to overcome certain PLE variants, and the mechanism of this immunity against PLE has thus far remained unknown. Here we show that ICP1 isolates that lack CRISPR-Cas encode an endonuclease in the same locus, and that the endonuclease provides ICP1 with immunity to a subset of PLEs. Further analysis shows that this endonuclease is of chimeric origin, incorporating a DNA binding domain that is highly similar to some PLE replication origin binding proteins. This similarity allows the endonuclease to bind and cleave PLE origins of replication. The endonuclease appears to exert considerable selective pressure on PLEs and may drive PLE replication module swapping and origin restructuring as mechanisms of escape. This work demonstrates that new genome defense systems can arise through domain shuffling and provides a greater understanding of the evolutionary forces driving genome modularity and temporal succession in mobile elements.
Genome-wide transcriptional responses of marine nematodeLitoditis marinato hyposaline and hypersaline stresses
Authors: Xie Yusu , Zhang Pengchi , Zhang Liusuo 
Published: February 2021

AbstractMaintenance of osmotic homeostasis is essential for all organisms, especially for marine animals in the ocean with 30‰ salinity or higher. However, the underlying molecular mechanisms that how marine animals adapt to high salinity environment compared to their terrestrial relatives, remain elusive. Here, we investigated marine animal’s genome-wide transcriptional responses to salinity stresses using an emerging marine nematode modelLitoditis marina. We found that the transthyretin-like family genes were significantly increased in both hyposaline and hypersaline conditions, while multiple neurotransmitter receptor and ion transporter genes were down-regulated in both conditions, suggesting the existence of conserved strategies for response to stressful salinity environments inL. marina. Unsaturated fatty acids biosynthesis related genes, neuronal related tubulins and intraflagellar transport genes were specifically up-regulated in hyposaline treated worms, while exhibited the opposite regulation in hypersaline condition. By contrast, cuticle related collagen genes were enriched and up-regulated for hypersaline response, interestingly, the expression of these collagen genes was significantly decreased in hyposaline condition. Given a wide range of salinity tolerance of the marine nematodes, this study and further genetic analysis of key gene(s) of osmoregulation inL. marinawill likely provide important insights into biological evolution and environmental adaptation mechanisms in nematodes and other invertebrate animals in general.
bMSI-CAST: a systematic method for next generation sequencing-based microsatellite instability detection in plasma cell-free DNA
Authors: Huang Fengchang , Zhao Lili , Xie Hongyu , Huang Jian , Wang Xiaoqing , Yang Jun , Hong Yuanyuan , Shu Jingchao , Yu Jianing , Li Qingyun , Zhang Hongbin , Chen Weizhi , He Ji , Li Wenliang 
Published: February 2021

ABSTRACTMicrosatellite instability (MSI) is a well-established prognostic and predictive biomarker in certain types of cancers. MSI detection using tumour tissue is often limited by the availability of specimens. Next generation sequencing (NGS)-based MSI detection in plasma cell-free DNA (cfDNA) is challenged by a much lower signal-to-noise ratio. We developed a highly accurate cfDNA MSI detection method called bMSI-CAST (blood MSI Caller Adjusted with Sequence duplicaTes), with improvement on three features including a set of locus selection principles ensuring loci with high robustness and compatibility across sequencing platforms, an MSI-specific duplicate removal strategy, and a calling algorithm that dynamically matches baselines with a broad range of duplication levels. Analytical validation via MSI-high (MSI-H) cell gDNA showed an LOD of 0.15%. Furthermore, in an analysis of 95 evaluable cfDNA samples from patients with gastrointestinal cancers, bMSI-CAST exhibited a positive predictive agreement (PPA) of 92.9% (39/42) and negative predictive agreement (NPA) of 100% (53/53) with tissue MSI-PCR. In conclusion, bMSI-CAST provides novel and advanced solutions to key aspects fundamental to cfDNA MSI calling but not sufficiently addressed by existing methods, and it is a validated method ready to be applied to aid clinical decisions for cancer patients.
Dynamic Predictive Coding with Hypernetworks
Authors: Jiang Linxing Preston , Gklezakos Dimitrios C. , Rao Rajesh P. N. 
Published: February 2021

AbstractThe original predictive coding model of Rao & Ballard [1] focused on spatial prediction to explain spatial receptive fields and contextual effects in the visual cortex. Here, we introduce a new dynamic predictive coding model that achieves spatiotemporal prediction of complex natural image sequences using time-varying transition matrices. We overcome the limitations of static linear transition models (as in, e.g., Kalman filters) using a hypernetwork to adjust the transition matrix dynamically for every time step, allowing the model to predict using a time-varying mixture of possible transition dynamics. We developed a single level model with recurrent modulation of transition weights by a hypernetwork and a two-level hierarchical model with top-down modulation based on a hypernetwork. At each time step, the model predicts the next input and estimates a sparse neural code by minimizing prediction error. When exposed to natural movies, the model learned localized, oriented spatial filters as well as both separable and inseparable (direction-selective) space-time receptive fields at the first level, similar to those found in the primary visual cortex (V1). Longer timescale responses and stability at the second level also emerged naturally from minimizing prediction errors for the first level dynamics. Our results suggest that the multiscale temporal response properties of cortical neurons could be the result of the cortex learning a hierarchical generative model of the visual world with higher order areas predicting the transition dynamics of lower order areas.
CCM2 deficient endothelial cells undergo a mechano-dependent reprogramming into senescence associated secretory phenotype used to recruit endothelial and immune cells
Authors: Vannier Daphné Raphaëlle , Shapeti Apeksha , Chuffart Florent , Planus Emmanuelle , Manet Sandra , Rivier Paul , Destaing Olivier , Albiges-Rizo Corinne , Van Oosterwyck Hans , Faurobert Eva 
Published: February 2021

AbstractCerebral Cavernous Malformations (CCM) is a cerebrovascular disease in which stacks of dilated haemorrhagic capillaries form focally in the brain. Whether and how defective mechanotransduction, cellular mosaicism and inflammation interplay to sustain the progression of CCM diseases is unknown. Here, we reveal that CCM1- and CCM2-silenced endothelial cells enter into senescence associated with secretory phenotype (SASP) that they use to invade the extracellular matrix and attract surrounding wild-type endothelial and immune cells. Further, we demonstrate that this SASP is driven by the mechanical and molecular disorders provoked by ROCKs dysfunctions. By this, we identify CCM1/2 and ROCKs as parts of a scaffold controlling senescence, bringing new insights into the emerging field of the control of aging by cellular mechanics. This discovery reconciles the dysregulated traits of CCM1/2-deficient endothelial cells into a unique mechano-dependent endothelial fate that links perturbed mechanics to microenvironment remodelling and long-range activation of endothelial and immune cells.
Physically interacting beta-delta pairs in the regenerating pancreas revealed by single-cell sequencing
Authors: Yanowski Eran , Yacovzada Nancy-Sarah , David Eyal , Giladi Amir , Jaitin Diego , Farack Lydia , Egozi Adi , Ben-Zvi Danny , Itzkovitz Shalev , Amit Ido , Hornstein Eran 
Published: February 2021

AbstractThe endocrine pancreas is able to regenerate in response to insult, including by driving beta-cells into the cell division cycle. Until recently, communication between neighboring cells in islets of Langerhans was overlooked by single-cell genomic technologies, which require rigorous tissue dissociation into single cells. Here, we utilize sorting of physically interacting cells (PICs) with single-cell RNA-sequencing to systematically map cellular interactions in the regenerating endocrine pancreas. The cellular landscape of the regenerated pancreas features regeneration-associated endocrine populations.We explore the unexpected heterogeneity of beta-cells in regeneration, including an interaction-specific program between paired beta and delta-cells. Our analysis suggests that the particular cluster of beta-cells that pair with delta-cells benefits from stress protection, implying that the interaction between beta and delta-cells safeguards against regeneration-associated challenges.
Key performance indicators for turboelectric distributed propulsion
Authors: Alrashed Mosab , Nikolaidis Theoklis , Pilidis Pericles , Jafari Soheil , Alrashed Wael 
Published: February 2021

PurposeRecent advancements in electrified transportation have been necessitated by the need to reduce environmentally harmful emissions. Accordingly, several aviation organisations and governments have introduced stringent emission reduction targets for 2050. One of the most promising technologies proposed for achieving these targets is turboelectric distributed propulsion (TeDP). The objective of this study was to explore and identify key indicators for enhancing the applicability of TeDP in air transportation.Design/methodology/approachAn enhancement valuation method was proposed to overcome the challenges associated with TeDP in terms of technological, economic and environmental impacts. The result indicators (RIs) were determined; the associated performance indicators (PIs) were analysed and the key RIs and PIs for TeDP were identified. Quantitative measurements were acquired from a simulated TeDP case study model to estimate the established key PIs.FindingsIt was determined that real-world TeDP efficiency could be enhanced by up to 8% by optimising the identified key PIs.Originality/valueThis study is the first to identify the key PIs of TeDP and to include a techno-economic environmental risk analysis (TERA) based on the identified key PIs. The findings could guide developers and researchers towards potential focus areas to realise the adoption of TeDP.
Stakeholder participation in Lopburi Old Town conservation master plan
Authors: Sorat Tritsana , Rawangkarn Nug-Rob , Rawang Wee , Kantamaturapoj Kanang 
Published: February 2021

PurposeThis study aims to evaluate the meaningful public participation in activities relating to the master plan development and, at the same time, propose some recommendations for improvement.Design/methodology/approachThe study was carried out with in-depth interviews of 35 key-informants selected from various stakeholder groups involving in public participation activities. The evaluation frameworks for meaningful participation were developed from various scholars.FindingsThe evaluation showed that the public hearings partially met the criteria of information provision and representativeness. However, there are rooms for improvement on participation in decision-making process, social learning and influence over policy decision-making. Therefore, this study proposes two recommendations. First, more flexible form of public participation is needed to enable discussions among various groups of stakeholders. Second, the organizer should communicate with stakeholders about how their opinions influence the final master plan in order to create sense of belonging among community members.Originality/valueThis research developed the evaluation framework for public participation in old town conservation master plan in developing country.
Does insourcing of processes pay off?
Authors: Grela Grzegorz , Hofman Mariusz 
Published: February 2021

Purpose
This study aims to examine whether insourcing of processes pays off and verifies key hypotheses regarding the financial ratios of organisations.

Design/methodology/approach
This paper randomly selects and then surveys 1996 organisations, of which 9.5% (190) stated that they used insourcing, 1.9% (37) made a decision to implement insourcing in the near future and 88.6% did not use insourcing. Then, for available firm data (100 insourcing firms and 100 firms without it), the financial statements of the surveyed companies were obtained to compare the most important financial ratios. The financial situation was compared at four-time points. The mean and median values of individual indicators were compared with the significance of relevant statistical tests.

Findings
A U-shaped curve of financial results in the time of enterprises that implemented insourcing and reverse U-shaped curve for enterprises that did not have insourcing are seen. Thus, the insourcing of processes pays off in the long run.

Research limitations/implications
Limitations exist in the generalisation of the results obtained, due to the limited number of samples qualified for analyses (limited reliable financial data).

Practical implications
The research highlights the importance of effective insourcing projects in the long term.

Originality/value
This study is the first to quantify the financial performance of companies that have used insourcing in comparison with a reference group. This paper defines insourcing and contributes to the growing number of studies on insourcing by bringing attention to the financial outcomes in the long run.
The suffering of refugees in Ghassan Kanafani’s “The Child Goes to the Camp”: a critical appraisal
Authors: Abdel Meguid Rania Mohammed Abdel 
Published: February 2021

Purpose
This paper aims to present a critical appraisal of Ghassan Kanafani’s short story “The Child Goes to the Camp” using the Appraisal Theory proposed by Martin and Rose (2007) in an attempt to investigate the predicament of the Palestinians who were forced to flee their country and live in refugee camps as well as the various effects refugee life had on them.

Design/methodology/approach
Using the Appraisal Theory, and with a special focus on the categories of Attitude and Graduation, the paper aims to shed light on the plight of refugees through revealing the narrator’s suffering in a refugee camp where the most important virtue becomes remaining alive.

Findings
Analysing the story using the Appraisal Theory reveals the impact refugee life has left on the narrator and his family. This story serves as a warning for the world of the suffering refugees have to endure when they are forced to flee their war-torn countries.

Originality/value
Although Kanafani’ resistance literature has been studied extensively, his short stories have not received much scholarly attention. In addition, his works have not been subject to linguistic analysis. This study presents an appraisal analysis of Kanafani’s “The Child Goes to the Camp” in an attempt to investigate how the author’s linguistic choices are key to highlighting the suffering of the Palestinians, especially children, in refugee camps.
Real-time polling to help corral university-learners' wandering minds
Authors: Price Trevor John 
Published: February 2021

PurposeThis research investigates the use of real-time online polling to enhance university teaching and learning.Design/methodology/approachUsing a case study and employing action research, this work shows how polling can improve professional practice, learner engagement and teaching performance.FindingsIncorporating the right type of online real-time polling into lessons is a professional challenge and can be hard work for teachers but has overriding benefits.Research limitations/implicationsThis research reports one lecturer's experiences within two UK universities, limited to location, variety of students and lecturer technical capability. The research implications are that online polling, especially in different learning environments, is needed. Previous research is outdated or limited to real-time polling for teaching and learning during physical classes. There are research opportunities therefore in the use of polling before, during and after class.Practical implicationsThis research finds that the field of online polling needs to be seen as a modern teaching tool that now uses students' personal technology for easier use by students and teachers: it is more than the use of archaic “clickers” which were extra classroom items to be bought and maintained. Also, online polling, before, during and after classes, can be employed usefully and have validity within teachers' toolboxes. This paper shows how such polls can be successfully deployed.Originality/valueWhilst there are previous reports of polling undertaken within teaching and learning events, this paper builds upon those experiences and boosts collective understanding about the use of polling as a way to improve professional practice and increase learning.