bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glisson’s capsule structure and function is altered in cirrhotic patients irrespective of etiology
Authors: Llewellyn Jessica , Fede Caterina , Loneker Abigail E. , Friday Chet S. , Hast Michael W. , Theise Neil D. , Furth Emma E. , Guido Maria , Stecco Carla , Wells Rebecca G. 
Published: August 2022

AbstractBackground and AimsGlisson’s capsule is the interstitial connective tissue that surrounds the liver. As part of its normal physiology, it withstands significant daily changes in liver size. The pathophysiology of the capsule in disease is not well understood. The aim of this study was to characterize the changes in capsule matrix, cellular composition, and mechanical properties that occur in liver disease and to determine whether these correlate with disease severity or etiology.Methods10 control, 6 steatotic, 7 moderately fibrotic and 37 cirrhotic patient samples were collected from autopsies, intraoperative biopsies and liver explants. Matrix proteins and cell markers were assessed by staining and second harmonic generation imaging. Mechanical tensile testing was performed on a test frame.ResultsCapsule thickness was significantly increased in cirrhotic samples compared to normal controls irrespective of disease etiology (69.62 ± 9.99 and 171.269 ± 16.65 µm respectively), whereas steatosis and moderate fibrosis had no effect on thickness (62.15 ± 4.97 µm). Changes in cirrhosis included an increase in cell number (fibroblasts, vascular cells, infiltrating immune cells and biliary epithelial cells). Key matrix components (collagens 1 and 3, hyaluronan, versican and elastin) were all deposited in the lower capsule although only the relative amounts per area of hyaluronan and versican were increased. Organizational features including crimping and alignment of collagen fibers were also altered in cirrhosis. Unexpectedly, capsules from cirrhotic livers had decreased resistance to loading in comparison to controls.ConclusionsThe liver capsule, like the parenchyma, is an active site of disease, demonstrating changes in matrix and cell composition as well as mechanical properties.Lay summaryWe assessed the changes in composition and response to stretching of the liver outer sheath, the capsule, in human liver disease. We find an increase in key structural components and numbers of cells as well as a change in matrix organization of the capsule in the later stages of disease. This allows the diseased capsule to stretch more under any given force, suggesting it is less stiff than healthy tissue.Graphical abstractHighlightsThe capsule is an active site of disease: thickness and cellularity increase markedly in cirrhosisExtracellular matrix composition and organization change in cirrhosisThe cirrhotic capsule stretches more and is less stiff
Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β-catenin signaling and tumor growth
Authors: Azbazdar Yagmur , Demirci Yeliz , Heger Guillaume , Karabicici Mustafa , Ozhan Gunes 
Published: August 2022

AbstractHepatocellular carcinoma (HCC) is largely associated with aberrant activation of Wnt/β-catenin signaling. Nevertheless, how membrane lipid composition is altered in HCC cells with abnormal Wnt signaling remains elusive. Here, by exploiting comprehensive lipidome profiling, we unravel membrane lipid composition of six different HCC cell lines with mutations in components of Wnt/β-catenin signaling, leading to differences in their endogenous signaling activity. Among the differentially regulated lipids are diacylglycerol (DAG) and ceramide, which were downregulated at the membrane of HCC cells after Wnt3a stimulation. DAG and ceramide enhanced Wnt/β-catenin signaling in SNU475 and HepG2 cells. In contrast, depletion of DAG and ceramide suppressed Wnt/β-catenin signaling and significantly impeded the proliferation, tumor growth and in vivo migration capacity of SNU475 and HepG2 cells. This study, by pioneering plasma membrane lipidome profiling in HCC cells, exhibits the remarkable potential of lipids to correct dysregulated signaling pathways in cancer and stop abnormal tumor growth.
Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization
Authors: Berquez Marine , Chen Zhiyong , Festa Beatrice Paola , Krohn Patrick , Keller Svenja Aline , Parolo Silvia , Korzinkin Mikhail , Gaponova Anna , Laczko Endre , Domenici Enrico , Devuyst Olivier , Luciani Alessandro 
Published: August 2022

AbstractDifferentiation is critical for cell fate decisions, but the signals involved remain unclear. The kidney proximal tubule (PT) cells reabsorb disulphide-rich proteins through endocytosis, generating cystine via lysosomal proteolysis. Here we report that defective cystine mobilization from lysosomes through cystinosin (CTNS), which is mutated in cystinosis, diverts PT cells towards growth and proliferation, disrupting their functions. Mechanistically, cystine storage stimulates Ragulator-Rag GTPase-dependent recruitment of mechanistic target of rapamycin complex 1 (mTORC1) and its constitutive activation. Re-introduction of CTNS restores nutrient-dependent regulation of mTORC1 in knockout cells, whereas cell-permeant analogues of L-cystine, accumulating within lysosomes, render wild-type cells resistant to nutrient withdrawal. Therapeutic mTORC1 inhibition corrects lysosome and differentiation downstream of cystine storage, and phenotypes in a zebrafish model of cystinosis. Thus, cystine serves as a lysosomal signal that tailors mTORC1 and metabolism to direct epithelial cell fate decisions. These results identify mechanisms and therapeutic targets for dysregulated homeostasis in cystinosis.
Variation in density, immune gene suppression, and co-infection outcomes among strains of the aphid endosymbiont Regiella insecticola
Authors: Goldstein Elliott B. , de Anda Acosta Yazmin , Henry Lee M. , Parker Benjamin J. 
Published: August 2022

AbstractMany insects harbor heritable beneficial microbes that influence host phenotypes. Across systems, divergent symbiont strains have been shown to establish at different densities within hosts. This genetic variation is important evolutionarily because within-host density has been linked to the costs and benefits of the symbiosis for both partners. Studying the factors shaping within-host density is therefore important to our broader understanding of host-microbe coevolution. Here we focused on different strains of Regiella insecticola, a facultative symbiont of aphids. We first demonstrated that different strains of Regiella consistently establish in pea aphids at drastically different densities. We then found that variation in density is correlated with the expression levels of two key insect immune system genes (phenoloxidase and hemocytin), with immune gene suppression correlating with higher Regiella density. We then performed an experiment where we established co-infections of a higher- and lower-density Regiella strain, and we showed that the higher-density strain is better able to persist in co-infections than the lower-density strain. Together, our results point to a potential mechanism for strain-level variation in symbiont density in this system, and further suggest that symbiont fitness may be increased by establishing at higher density within hosts. Our work highlights the importance of within-host dynamics shaping symbiont evolution.
Characterization of factors that underlie transcriptional silencing inC. elegansoocytes
Authors: Belew Mezmur D. , Chien Emilie , Michael W. Matthew 
Published: August 2022

Abstract/SummaryWhile it has been appreciated for decades that prophase-arrested oocytes are transcriptionally silenced on a global level, the molecular pathways that promote silencing have remained elusive. Previous work inC. eleganshas shown that both topoisomerase II (TOP-2) and condensin II collaborate with the H3K9me heterochromatin pathway to silence gene expression in the germline during L1 starvation, and that the PIE-1 protein silences the genome in the P-lineage of early embryos. Here, we show that all three of these silencing systems, TOP-2/condensin II, H3K9me, and PIE-1, are required for transcriptional repression in oocytes. We find that H3K9me3 marks increase dramatically on chromatin during silencing, and that silencing is under cell cycle control. We also find that PIE-1 localizes to the nucleolus just prior to silencing, and that nucleolar dissolution during silencing is dependent on TOP-2/condensin II. Our data identify both the molecular components and the trigger for genome silencing in oocytes and establish a link between PIE-1 nucleolar residency and its ability to repress transcription.
Genomic and phenotypic evolution of nematode-infecting microsporidia
Authors: Wadi Lina , El Jarkass Hala Tamim , Tran Tuan D. , Islah Nizar , Luallen Robert J. , Reinke Aaron W. 
Published: August 2022

AbstractMicrosporidia are a large phylum of intracellular parasites that can infect most types of animals. Species in theNematocidagenus can infect nematodes includingCaenorhabditis elegans, which has become an important model to study mechanisms of microsporidia infection. To understand the genomic properties and evolution of nematode-infecting microsporidia, we sequenced the genomes of nine species of microsporidia, including two genera,EnteropsectraandPancytospora,without any previously sequenced genomes. Core cellular processes, including metabolic pathways, are mostly conserved across genera of nematode-infecting microsporidia. Each species encodes unique proteins belonging to large gene families that are likely used to interact with host cells. Most strikingly, we observed one such family, NemLGF1, is present in bothNematocidaandPancytosporaspecies, suggesting horizontal gene transfer between species from different genera. To understand howNematocidaphenotypic traits evolved, we measured the host range, tissue specificity, spore size, and polar tube length of several species in the genus. Our phylogenetic analysis shows thatNematocidais composed of two groups of species with distinct traits and that species with longer polar tubes infect multiple tissues. Together, our work details both genomic and trait evolution between related microsporidia species and provides a useful resource for further understanding microsporidia evolution and infection mechanisms.Author SummaryMicrosporidia are microbial parasites that can infect many animals. Nematodes have become a useful system to study microsporidia as these animals are commonly infected by microsporidia and these infections can be easily studied in a laboratory environment. To better understand how microsporidia evolve and change their properties as they infect different hosts, we sequenced the genomes of nine microsporidia species which infect nematodes. We found that metabolic pathways were mostly conserved between different clades of these species. Surprisingly, we found a family of proteins predicted to facilitate host interactions that is present in two distinct genera, suggesting that these genes were transferred between microsporidia species. We also determined the hosts and tissues that these microsporidia can infect as well as morphological properties of the microsporidia. We show that these properties are quite variable in related microsporidia species. Our results provide insight into the evolution of microsporidia and also provide a resource for studying microsporidia infections in nematodes.
Promyelocytic Leukemia Protein regulates Angiogenesis and Epithelial-Mesenchymal Transition to limit metastasis in MDA-MB-231 breast cancer cells
Authors: Vogiatzoglou Amalia P , Spanou Syrago , Sachini Nikoleta , Drakos Elias , Nikolaou Christoforos , Makatounakis Takis , Kretsovali Androniki , Papamatheakis Joseph 
Published: August 2022

ABSTRACTPromyelocytic Leukemia Protein (PML) is the core protein of nuclear bodies (NBs) that regulate a large number of cellular processes, including, context dependent, tumor –suppressor and pro-oncogenic effects. PML knockdown (KD) in breast cancer lines MDA-MB-231, but not MCF7, cells showed higher cell proliferation, increased migration properties and prolonged stem cell –like survival in line with gene enrichment results from RNA sequencing analysis. MDA-MB-231 PML KD cells showed an increase of hypoxic and mesenchymal characteristics manifested by higher HIF1a and the EMT-TWIST2 protein levels respectively. Mechanistically, PML loss caused an increase of HIF1a and TWIST2 RNA levels. Interestingly, TWIST2 binds to PML. Moreover, PML directly opposed the action of HIF1a and TWIST2 on VEGFa and CD24 reporters, respectively. Tumor xenografts of MDA-MB-231 PML KD cells showed a higher micro vessel content, grew faster and had higher metastatic ability with a preference for lung. Thus, PML opposes the aggressive cancer phenotype by multiple mechanisms that antagonize the HIF-hypoxia-angiogenic and EMT axis.
Addressing the challenges of symbiont-mediated RNAi in aphids
Authors: Elston Katherine M. , Maeda Gerald P. , Perreau Julie , Barrick Jeffrey E. 
Published: August 2022

AbstractBecause aphids are global agricultural pests and models for bacterial endosymbiosis, there is a need for reliable methods to study and control their gene function. However, current methods available for aphid gene knockout and knockdown of gene expression are often unreliable and time consuming. Techniques like CRISPR-Cas genome editing can take several months to achieve a single gene knockout because they rely on aphids going through a cycle of sexual reproduction, and aphids often lack strong, consistent levels of knockdown when fed or injected with molecules that induce an RNA interference (RNAi) response. In the hopes of addressing these challenges, we attempted to adapt a new method called symbiont-mediated RNAi (smRNAi) for use in aphids. smRNAi involves engineering a bacterial symbiont of the insect to continuously supply dsRNA inside the insect body. This approach has been successful in thrips, kissing bugs, and honeybees. We engineered the laboratory E. coli strain HT115 and the native aphid symbiont S. symbiotica CWBI-2.3T to produce dsRNA inside the gut of the pea aphid (Acyrthosiphon pisum) targeting salivary effector protein (C002) or ecdysone receptor genes. For C002 assays, we also tested co-knockdown with an aphid nuclease (Nuc1) to reduce RNA degradation. However, we found that smRNAi was not a reliable method for aphid gene knockdown under our conditions. We were unable to consistently achieve the expected phenotypic changes with either target. However, we did see indications that elements of the RNAi pathway were modestly upregulated, and expression of some targeted genes appeared to be somewhat reduced in some trials. We conclude with a discussion of the possible avenues through which smRNAi, and aphid RNAi in general, could be improved in the future.
Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia
Authors: Beneyto-Calabuig Sergi , Ludwig Anne Kathrin , Kniffka Jonas-Alexander , Szu-Tu Chelsea , Rohde Christian , Antes Magdalena , Waclawiczek Alexander , Gräßle Sarah , Pervan Philip , Janssen Maike , Landry Jonathan J. M. , Benes Vladimir , Jauch Anna , Brough Michaela , Bauer Marcus , Besenbeck Birgit , Felden Julia , Bäumer Sebastian , Hundemer Michael , Sauer Tim , Pabst Caroline , Wickenhauser Claudia , Angenendt Linus , Schliemann Christoph , Trumpp Andreas , Haas Simon , Scherer Michael , Raffel Simon , Müller-Tidow Carsten , Velten Lars 
Published: August 2022

AbstractInter-patient variability and the similarity of healthy and leukemic stem cells have impeded the characterization of leukemic stem cells (LSCs) in acute myeloid leukemia (AML), and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. While residual healthy cells dominated the dormant stem cell compartment, active leukemic stem cells resembled their healthy counterpart and retained erythroid capacity. By contrast, downstream myeloid progenitors were highly aberrant and constituted the disease-defining compartment: Their gene expression and differentiation state determined both chemotherapy response and the leukemia’s ability to differentiate to transcriptomically normal monocytes. Finally, we demonstrated the potential of CloneTracer to identify surface markers mis-regulated specifically in leukemic cells by intra-patient comparisons. Taken together, CloneTracer revealed a differentiation landscape that mimics its healthy counterpart and determines biology and therapy response in AML.
Positive addiction recovery therapy: a pilot study
Authors: Ogilvie Lisa , Carson Jerome 
Published: August 2022

PurposeThe purpose of this study is to evaluate a new programme of work designed to improve the recovery and well-being of people in early addiction recovery. The programme, known as positive addiction recovery therapy (PART), is attentive to the recovery process through the G-CHIME (growth, connectedness, hope, identity, meaning in life and empowerment) model of addiction recovery. It also uses the values in action character strengths and includes a set of relapse prevention techniques.Design/methodology/approachAn experimental design using repeated measures has been adopted. Measures for recovery capital, well-being and level of flourishing were selected and pre- and post-data collected. Primary data analysis was conducted using the non-parametric Wilcoxon signed-rank test. Participants (n= 30) were required to be in early addiction recovery, classified as having been abstinent for between three and six months.FindingsThe results showed a statistically significant improvement in participant well-being. This was also true for recovery capital and flourishing. Whilst a meaningful increase was seen in all measures, exploratory analysis found females responded better to the PART programme.Practical implicationsThis study emphasises the importance of adopting a holistic therapeutic approach, one that considers multifaceted components of recovery such as those outlined in the G-CHIME model.Originality/valueThis study evaluates a new programme of work designed to improve the recovery outcome and mental well-being of people who are in early addiction recovery.
Ground effect on the aerodynamics of a flapping wing in forward flight: an experimental study
Authors: Arasteh Mostafa , Azargoon Yegane , Djavareshkian M.H. 
Published: August 2022

Purpose
Ground effect is one of the important factors in the enhancement of wing aerodynamic performance. This study aims to investigate the aerodynamic forces and performance of a flapping wing with the bending deflection angel under the ground effect.

Design/methodology/approach
In this study, the wing and flapping mechanism were designed and manufactured based on the seagull flight and then assembled. It is worth noting that this mechanism is capable of wing bending in the upstroke flight as big birds. Finally, the model was examined at bending deflection angles of 0° and 107° and different distances from the surface, flapping frequencies and velocities in forward flight in a wind tunnel.

Findings
The results revealed that the aerodynamic performance of flapping wings in forward flight improved due to the ground effect. The effect of the bending deflection mechanism on lift generation was escalated when the flapping wing was close to the surface, where the maximum power loading occurred.

Practical implications
Flapping wings have many different applications, such as maintenance, traffic control, pollution monitoring, meteorology and high-risk operations. Unlike fixed-wing micro aerial vehicles, flapping wings are capable of operating in very-low Reynolds-number flow regimes. On the other hand, ground effect poses positive impacts on the provision of aerodynamic forces in the take-off process.

Originality/value
Bending deflection in the flapping motion and ground effect are two influential factors in the enhancement of the aerodynamic performance of flapping wings. The combined effects of these two factors have not been studied yet, which is addressed in this study.
Is newer better? Evaluating the suitability of nighttime luminosity in proxying poverty in Africa
Authors: Hamman Nicolene , Phiri Andrew 
Published: August 2022

PurposeThe purpose of the study is to evaluate whether nighttime luminosity sourced from the Defense Meteorological Satellite Program-Operational Linescan System satellite sensors is a suitable proxy for measuring poverty in Africa.Design/methodology/approachOur study performs wavelet coherence analysis to investigate the time-frequency synchronization between the nightlight data and “income-to-wealth” ratio for 39 African countries between 1992 and 2012.FindingsAll-in-all, the authors find that approximately a third of African countries produce positive synchronizations between nighttime data and “income-to-wealth” ratio and hence conclude that most African countries are not at liberty to use nighttime data to proxy conventional poverty statistics.Originality/valueIn differing from previous studies, the authors examine the suitability of nightlight intensity as a proxy of poverty for individual African countries using much more rigorous analysis.
The corporate governance-diversification link: exploring the heterogeneity of family firms
Authors: Galavotti Ilaria , D'Este Carlotta 
Published: August 2022

Purpose
Building on behavioral agency theory, the authors explore the role played by corporate governance characteristics as drivers of the diversification strategies of family firms. Specifically, this study aims to investigate the effects of board size and board gender diversity on the likelihood that family firms will execute a diversifying acquisition vis-à-vis a related acquisition. Furthermore, the authors investigate the contingency effects played by foreign directorship and the firm’s listing status.

Design/methodology/approach
The hypotheses are tested on an original sample of 213 cross-border acquisitions executed by Italian family firms between 2008 and 2021.

Findings
The findings suggest that both large board sizes and greater gender diversity positively affect the diversification of family firms. While the presence of foreign directors magnifies the positive effect of board size, gender diversity discourages diversification in the case of listed firms.

Originality/value
The originality of this study is twofold. First, while prior literature has mostly focused on the family vs nonfamily dichotomy, this paper contributes to an emergent line of research investigating the heterogeneity among family firms’ corporate strategy decisions. Second, by exploring the corporate governance-diversification link in the context of family business, the authors answer to recent calls that diversification by family firms deserves further investigation in light of its highly controversial nature in terms of socioemotional wealth implications and potential mismatch among multiple objectives.