bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular Endothelial Cells Perform Distinct Sensing and Signaling of Laminar and Disturbed Flows across Plasma Membranes and Mitochondria
Authors: Yamamoto Kimiko , Maeno Ryohei , Kawabe Kenshiroh , Shimogonya Yuji , Ando Joji 
Published: April 2023

AbstractBACKGROUNDVascular endothelial cells (ECs) experience two different blood flow patterns: laminar and disturbed flows. Their responses to laminar flow contribute to vascular homeostasis, whereas their responses to disturbed flow result in EC dysfunction and vascular diseases. However, it remains unclear how ECs differentially sense laminar and disturbed flows and trigger signalings that elicit different EC responses. We aimed to investigate EC flow-sensing and signaling mechanisms, focusing on the role of the plasma membrane and mitochondria.METHODSWe exposed cultured human aortic ECs to laminar flow and disturbed flow in flow-loading devices and used real-time imaging with optical probes to examine changes in the lipid order of the plasma and mitochondria membranes and the mitochondrial adenosine triphosphate (ATP) production and hydrogen peroxide (H2O2) release.RESULTSThe lipid order of EC plasma membranes immediately decreased in response to laminar flow, while it increased in response to disturbed flow. Laminar flow also decreased the lipid order of mitochondrial membranes and increased mitochondrial ATP production. In contrast, disturbed flow increased the lipid order of mitochondrial membranes and increased the release of H2O2from mitochondria. Addition of cholesterol to the cells increased the lipid order of both membranes and abrogated the laminar flow-induced ATP production, while treatment of the cells with a cholesterol-depleting reagent, methyl-β cyclodextrin, decreased the lipid order of both membranes and abolished the disturbed flow-induced H2O2release, indicating that the changes in the membrane lipid order are closely linked to the flow-induced changes in the mitochondrial functions.CONCLUSIONSECs differentially sense laminar and disturbed flows by altering the lipid order of their plasma and mitochondrial membranes in opposite directions, which result in distinct changes in the mitochondrial functions, namely, increased ATP production for laminar flow and increased H2O2release for disturbed flow, leading to ATP- and H2O2-mediated signalings, respectively.
DCBLD1 modulates angiogenesis by regulating of the VEGFR-2 endocytosis in endothelial cells
Authors: Feng Qi , Guo Lingling , Yu Chao , Liu Xiaoning , Lin Yanling , Li Chenyang , Zhang Wenjun , Zong Yanhong , Yang Weiwei , Ma Yuehua , Wang Runtao , Li Lijing , Pei Yunli , Wang Huifang , Liu Demin , Han Mei , Niu Honglin , Nie Lei 
Published: April 2023

AbstractObjectiveUnwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (Discoidin, CUB, and LCCL domain-containing protein 1) is a co-receptor of VEGFR-2 and modulates angiogenesis in endothelial cells(ECs).Approach and ResultsA carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or EC-specific conditional DCBLD1 knockout micein vivo. Immunoblotting, immunofluorescence staining, plasma-membrane subfraction isolation, Co-immunoprecipitation and mass-spectrum assay were performed to clarify the molecular mechanisms.Loss of DCBLD1 impaired VEGF response and inhibited VEGF-induced EC proliferation and migration. DCBLD1 deletion interfered with adult and developmental angiogenesis. Mechanistically, DCBLD1 bound to VEGFR-2 and regulated the formation of VEGFR-2 complex with negative regulators: protein tyrosine phosphatases, E3 ubiquitin ligases(Nedd4 and c-Cbl), and also DCBLD1 knockdown promoted lysosome-mediated VEGFR-2 degradation in ECs.ConclusionsThese findings demonstrated the essential role of endothelial DCBLD1 in regulating VEGF signaling and provided evidence that DCBLD1 promotes VEGF-induced angiogenesis by limiting the dephosphorylation, ubiquitination, and lysosome degradation after VEGFR-2 endocytosis. We proposed that endothelial DCBLD1 is a potential therapeutic target for ischemic cardiovascular diseases by the modulation of angiogenesis through regulating of the VEGFR-2 endocytosis.
Putative NAD(P)-binding Rossmann fold protein is involved in chitosan-induced peroxidase activity and lipoxygenase expression in Physcomitrella
Authors: Marttinen Eeva M. , Decker Eva L. , Heinonen Petra , Reski Ralf , Valkonen Jari P.T. 
Published: April 2023

AbstractOxidative burst, the rapid production of high levels of reactive oxygen species (ROS) in response to external stimuli, is an early defense reaction against pathogens. The fungal elicitor chitosan causes an oxidative burst in the moss Physcomitrella (new species name:Physcomitrium patens) mainly due to the peroxidase enzyme Prx34. To better understand the chitosan responses in Physcomitrella, we conducted a screen of part of aP. patensmutant collection to isolate plants with less peroxidase activity than wild-type plants after chitosan treatment. We isolated aP. patensmutant that affected the gene encoding NAD(P)-binding Rossmann fold protein (hereafter, Rossmann fold protein). Three Rossmann fold protein-knockout (KO) plants (named Rossmann fold KO-lines) were generated and used to assess extracellular peroxidase activity and expression of defense-responsive genes including alternative oxidase (AOX), lipoxygenase (LOX), NADPH-oxidase (NOX) and peroxidase (Prx34) in response to chitosan treatment. Extracellular (apoplastic) peroxidase activity was significantly lower in Rossmann fold KO-lines than in wild-type plants after chitosan treatments. Expression of the LOX gene in Rossmann-fold KO-plants was significantly lower before and after chitosan treatment when compared to WT. Peroxidase activity assays together with gene expression analyses suggest that the Rossmann-fold protein might be an important component of the signaling pathway leading to oxidative burst and basal expression of the LOX gene in Physcomitrella.
Optimization of a Novel Automated, Low Cost, Three-Dimensional Photogrammetry System (PHACE)
Authors: To Josiah K. , Wang Jenny N. , Vu Anderson N. , Ediriwickrema Lilangi S. , Browne Andrew W. 
Published: April 2023

AbstractIntroductionClinical tools are neither standardized nor ubiquitous to monitor volumetric or morphological changes in the periorbital region and ocular adnexa due to pathology such as oculofacial trauma, thyroid eye disease, and the natural aging process. We have developed a low-cost, three dimensionally printedPHotogrammetry forAutomatedCarE(PHACE) system to evaluate three-dimensional (3D) measurements of periocular and adnexal tissue.MethodsThe PHACE system uses two Google Pixel 3 smartphones attached to automatic rotating platforms to image a subject’s face through a cutout board patterned with registration marks. Photographs of faces were taken from many perspectives by the cameras placed on the rotating platform. Faces were imaged with and without 3D printed hemispheric phantom lesions (black domes) affixed on the forehead above the brow. Images were rendered into 3D models in Metashape (Agisoft, St. Petersburg, Russia) and then processed and analyzed in CloudCompare (CC) and Autodesk’s Meshmixer. The 3D printed hemispheres affixed to the face were then quantified within Meshmixer and compared to their known volumes. Finally, we compared digital exophthalmometry measurements with results from a standard Hertel exophthalmometer in a subject with and without an orbital prosthesis.ResultsQuantification of 3D printed phantom volumes using optimized stereophotogrammetry demonstrated a 2.5% error for a 244μL phantom, and 7.6% error for a 27.5μL phantom. Digital exophthalmometry measurements differed by 0.72mm from a standard exophthalmometer.ConclusionWe demonstrated an optimized workflow using our custom apparatus to analyze and quantify oculofacial volumetric and dimensions changes with a resolution of 244μL. This apparatus is a low-cost tool that can be used in clinical settings to objectively monitor volumetric and morphological changes in periorbital anatomy.
Compartmentation of photosynthesis gene expression between mesophyll and bundle sheath cells of C4maize is dependent on time of day
Authors: Borba AR , Reyna-Llorens I , Dickinson PJ , Steed G , Gouveia P , Górska AM , Gomes C , Kromdijk J , Webb AAR , Saibo NJM , Hibberd JM 
Published: April 2023

AbstractCompared with the ancestral C3state, C4photosynthesis enables higher rates of photosynthesis as well as improved water and nitrogen use efficiencies. In both C3and C4plants rates of photosynthesis increase with light intensity and so are maximal around midday. We report that in the absence of light or temperature fluctuations, photosynthesis in maize peaks in the middle of the subjective photoperiod. To investigate molecular processes associated with these changes, we undertook RNA-sequencing of maize mesophyll and bundle sheath strands over a 24-hour time-course. Cell-preferential expression of C4cycle genes was strongest between six and ten hours after dawn when rates of photosynthesis were highest. For the bundle sheath, DNA motif enrichment and gene co-expression analyses suggested members of the DOF and MADS-domain transcription factor families mediate diurnal fluctuations in C4gene expression, andtrans-activation assaysin plantaconfirmed their ability to activate promoter fragments from bundle sheath expressed genes. The work thus identifies transcriptional regulators as well as peaks in cell-specific C4gene expression coincident with maximum rates of photosynthesis in the maize leaf at midday.
Kronos: A computational tool to facilitate biological rhythmicity analysis
Authors: Bastiaanssen Thomaz F. S. , Leigh Sarah-Jane , Tofani Gabriel S. S. , Gheorghe Cassandra E. , Clarke Gerard , Cryan John F. 
Published: April 2023

AbstractMotivationCircadian rhythms, or 24-hour biological cycles, are key in maintaining health in almost all living organisms and synchronize important physiological and behavioural processes daily. Interest in circadian rhythm research is expanding as our urban environments have increased exposure to factors that can disrupt the normal physiological rhythm of our body, such as delayed bedtimes, shift work, jet-lag, increased screen-time, and exposure to artificial light. Discovering how oscillatory signals respond to both external and internal factors can lead to important biological breakthroughs, but assessing rhythmicity can be both limited by the complexity of statistical models and demanding in terms of coding and statistical expertise.ImplementationHere, we describe the development of a novel easy-to-use R-based tool, Kronos, to assess circadian rhythms in biological data sets. Kronos provides the user with new functionalities not currently available, including the analysis of two or more groups in complex study designs, handling both independent and repeated-measures data, as well as ranging from single variables to high dimensional ‘omics data sets. Kronos is a novel tool to facilitate the analysis of rhythmicity in simple and complex experimental designs and enables researchers from diverse scientific fields to interrogate rhythmicity.Availabilityhttps://github.com/thomazbastiaanssen/kronos
Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period
Authors: Bolumar David , Moncayo-Arlandi Javier , Gonzalez-Fernandez Javier , Ochando Ana , Moreno Inmaculada , Monteagudo-Sanchez Ana , Marin Carlos , Diez Antonio , Fabra Paula , Checa Miguel Ángel , Espinos Juan José , Gardner David K. , Simon Carlos , Vilella Felipe 
Published: April 2023

SummaryThe transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. We aimed to investigate the potential for vertical DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics.We discovered that the human endometrium secretes all three general subtypes of EV - apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) - into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of mitochondrial (mt)DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived nuclear-encoded (n)DNA/mtDNA by trophoblast cells of murine embryos, which associates with a reduction in mitochondrial respiration and ATP production.These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that nDNA/mtDNA become packaged into secreted EVs that the embryo uptakes, and that the transfer of DNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation.
Cradle to production gate life cycle assessment of cultured meat growth media: A comparison of Essential 8™ and Beefy-9
Authors: Risner Derrick , Negulescu Patrick , Kim Yoonbin , Nguyen Cuong , Siegel Justin B. , Spang Edward S. 
Published: April 2023

AbstractThere is an increasing interest in use of biotechnology as a means of sustainable food manufacturing; however, biotechnology processing is considerably resource and energy intensive. Recent interest in animal cell-based meat (ACBM) has prompted scientific and engineering questions about the economic and environmental viability of these proposed ACBM products. This study provides an environmental assessment of two proposed growth mediums (Essential 8TMand Beefy-9) for ACBM production. The study found that the addition of antibiotics/antimycotics (10,000 μg/mL) to the growth media increased the environmental metrics, such as the cumulative energy demand and global warming potential, by two orders of magnitude. To account for additional processing for animal cell culture, a scenario analysis was conducted to assess the potential environmental impacts of growth medium production with varying level of refinement required for the input components. The study indicates that the heavy refinement of the growth medium components is likely to undermine the potential sustainability of future ACBM products.
RNA-binding protein YBX1 promotes Type H vessels dependent bone formation in an m5C-dependent manner
Authors: Li Yu-Jue , Guo Qi , Xiao Wen-Feng , Xiao Ye 
Published: April 2023

AbstractRNA Binding Proteins (RBPs) interact with RNA and ubiquitously regulating RNA transcripts during their life cycle. Previous works showed that RBPs play fundamental roles in the progression of angiogenesis-related diseases. However, the role of RBPs in skeletal endothelium-dependent bone formation and osteogenesis is unclear. Here, we show that RBP-Ybx1 was strongly reduced in bone vasculature from ovariectomy-induced osteoporotic mice. Endothelial cell-specific deletion of Ybx1 impaired CD31hiEMCNhiendothelium morphology and osteogenesis and resulted in low bone mass, while its overexpression promoted angiogenesis-dependent osteogenesis and ameliorated bone loss in OVX mice. Mechanistically, Ybx1 deletion disrupted CD31, EMCN and BMP4 stability in an m5C-dependent manner and blocked endothelial-derived BMP4 release, thereby inhibiting osteogenic differentiation of BMSCs. Administration of recombinant BMP4 protein promoted osteogenic differentiation of BMSCs and restored impaired bone formation in Ybx1iΔECmice. Finally, tail vein injection of CD31-modified PEG-PLGA carrying sciadopitysin, a natural Ybx1 agonist, pharmacologically partially reversed CD31hiEMCNhivessels decline and improved the restoration of bone mass both in OVX and aging animals. These findings demonstrated the role of RBP-Ybx1 in angiogenesis-dependent bone formation and provided a novel therapeutic approach for ameliorating aging-related and postmenopausal osteoporosis.
The architecture of metabolic networks constrains the evolution of microbial resource hierarchies
Authors: Takano Sotaro , Vila Jean CC , Miyazaki Ryo , Sanchez Alvaro , Bajic Djordje 
Published: April 2023

AbstractMicrobial strategies for resource use are an essential determinant of their fitness in complex habitats. When facing environments with multiple nutrients, microbes often use them sequentially according to a preference hierarchy, resulting in well-known patterns of diauxic growth. In theory, the evolutionary diversification of metabolic hierarchies could represent a mechanism supporting coexistence and biodiversity by enabling temporal segregation of niches. Despite this ecologically critical role, the extent to which substrate preference hierarchies can evolve and diversify remains largely unexplored. Here we used genome-scale metabolic modeling to systematically explore the evolution of metabolic hierarchies across a vast space of metabolic network genotypes. We find that only a limited number of metabolic hierarchies can readily evolve, corresponding to the most commonly observed hierarchies in genome-derived models. We further show how the evolution of novel hierarchies is constrained by the architecture of central metabolism, which determines both the propensity to change ranks between pairs of substrates and the effect of specific reactions on hierarchy evolution. Our analysis sheds light on the genetic and mechanistic determinants of microbial metabolic hierarchies, opening new research avenues to understand their evolution, evolvability and ecology.
TUMOR ENDOTHELIAL CELL AUTOPHAGY IS A KEY VASCULAR-IMMUNE CHECKPOINT IN MELANOMA
Authors: Verhoeven Jelle , Jacobs Kathryn A , Rizzollo Francesca , Lodi Francesca , Hua Yichao , Poźniak Joanna , Srinivasan Adhithya Narayanan , Houbaert Diede , Shankar Gautam , More Sanket , Schaaf Marco B , Lakic Nikolina Dubroja , Ganne Maarten , Lamote Jochen , Weyenbergh Johan Van , Boon Louis , Bechter Oliver , Bosisio Francesca , Bertrand Mathieu JM , Marine Jean Christophe , Lambrechts Diether , Bergers Gabriele , Agrawal Madhur , Agostinis Patrizia 
Published: April 2023

ABSTRACTTumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show that autophagy ablation in TECs boosts antitumor immunity by supporting infiltration and effector function of T cells, thereby restricting melanoma growth. In melanoma-bearing mice, loss of TEC autophagy leads to the transcriptional expression of an immunostimulatory/inflammatory TEC phenotype driven by heightened NF-kB and STING signaling. In line, single-cell transcriptomic datasets from melanoma patients disclose an enriched InflammatoryHigh/AutophagyLowTEC phenotype in correlation with clinical responses to immunotherapy. Congruently, patients responding to immunotherapy exhibit an increased presence of inflamed vessels, interfacing with infiltrating CD8+ T cells. Mechanistically, STING-dependent immunity in TECs is not critical for the immunomodulatory effects of autophagy ablation, since NF-kB-driven inflammation remains functional in STING/ATG5 double knockout TECs. Hence, autophagy is a principal tumor vascular anti-inflammatory mechanism dampening melanoma antitumor immunity.
The effect of developmental variation on expression QTLs in a multi parentalC. eleganspopulation
Authors: van Eijnatten Bram , Sterken Mark , Kammenga Jan , Nijveen Harm , Snoek Basten L. 
Published: April 2023

AbstractRegulation of gene expression plays a crucial role in the development and adaptation of organisms to changing environments. A population-based procedure used to investigate the genetic regulation of gene expression is eQTL mapping. Typically, the age of the population used for eQTL mapping at the time of sampling is strictly controlled. This is necessary because the developmental process causes changes in gene expression, complicating the interpretation of eQTL mapping experiments. However, organisms can differ in their “developmental age”, even if they are of the same chronological age. As a result, eQTL patterns are affected by uncontrolled developmental variation in gene expression. The model organismC. elegansis particularly suited for studying the effect of developmental variation on eQTL mapping patterns. In a span of daysC. eleganstransitions from embryo through four larval stages to adult while undergoing massive changes to its transcriptome. Here we useC. elegansto investigate the effect of developmental age variation on eQTL patterns and an available normalization procedure. We used dynamical eQTL mapping, which includes developmental age as a cofactor, to separate the variation in development from genotypic variation and explain variation in gene expression levels. We compare classical single marker eQTL mapping and dynamical eQTL mapping using RNA-seq data of ∼200 multi-parental recombinant inbred lines ofC. elegans. The results show that many eQTLs are actually caused by developmental variation, that most trans-bands are associated with developmental age and that dynamical eQTL mapping detects additional eQTLs not found with classical eQTL mapping.
Functional analysis ofSalix purpureagenes support roles forARR17andGATA15as master regulators of sex determination
Authors: Hyden Brennan , Carper Dana L. , Abraham Paul E. , Yuan Guoliang , Yao Tao , Baumgart Leo , Zhang Yu , Chen Cindy , O’Malley Ronan , Chen Jin-Gui , Yang Xiaohan , Hettich Robert L. , Tuskan Gerald A. , Smart Lawrence B. 
Published: April 2023

AbstractThe Salicaceae family is of growing interest in the study of dioecy in plants because the sex determination region (SDR) has been shown to be highly dynamic, with differing locations and heterogametic systems between species. Without the ability to transform and regenerateSalixin tissue culture, previous studies investigating the mechanisms regulating sex in the genusSalixhave been limited to genome resequencing and differential gene expression, which are mostly descriptive in nature, and functional validation of candidate sex determination genes has not yet been conducted. Here we used Arabidopsis to functionally characterize a suite of previously identified candidate genes involved in sex determination and sex dimorphism in the bioenergy shrub willowSalix purpurea. Six candidate master regulator genes for sex determination were heterologously expressed in Arabidopsis, followed by floral proteome analysis. In addition, 11 transcription factors with predicted roles in mediating sex dimorphism downstream of the SDR were tested using DAP-Seq in both male and femaleS. purpureaDNA. The results of this study provide further evidence to support models for the roles ofARR17andGATA15as master regulator genes of sex determination inS. purpurea, contributing to a regulatory system that is notably different from that of its sister genusPopulus. Evidence was also obtained for the roles of two transcription factors, anAP2/ERFfamily gene and a homeodomain-like transcription factor, in downstream regulation of sex dimorphism.