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Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation

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Bone Research 2018年第1期6卷 83-94页

作者： Heather A.carey Blake E.Hildreth III Jennifer A.Geisler Mara c.Nickel Jennifer cabrera Sankha Ghosh Yue Jiang Jing Yan James Lee Sandeep Makam Nicholas A.Young Giancarlo R.Valiente Wael N.Jarjour Kun Huang Thomas J.Rosol Ramiro E.Toribio Julia F.charles michael c.ostrowski Sudarshana M.Sharma Department of cancer Biology and Genetics and comprehensive cancer center The Ohio State University Wexner Medical Center college of Veterinary Medicine The Ohio State University Department of Biochemistry and Molecular Biology and Hollings cancer center Medical University of South Carolina Division of Rheumatology Immunology and Allergy Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Division of Rheumatology and Immunology Department of Internal Medicine The Ohio State University Wexner Medical Center Department of Biomedical Informatics The Ohio State University Wexner Medical Center

Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(Oc)-specific functions. Specifically, in Ocs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in Ocs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for Oc differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.

关键词： Genome-wide GWASs MITF

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Macroalgal deep genomics illuminate multiple paths to aquatic,photosynthetic multicellularity

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Molecular Plant 2024年第5期17卷 747-771页

作者： David R.Nelson Alexandra Mystikou Ashish Jaiswal cecilia Rad-Menendez michael J.Preston Frederik De Boever Diana c.El Assal Sarah Daakour michael W.Lomas Jean-claude Twizere David H.Green William c.Ratcliff Kourosh Salehi-Ashtiani Division of Science and Math New York University Abu DhabiAbu DhabiUAE center for Genomics and Systems Biology(cGSB) New York University Abu DhabiAbu DhabiUAE Biotechnology Research center Technology Innovation InstitutePO Box 9639Masdar CityAbu DhabiUAE culture collection of Algae and Protozoa Scottish Association for Marine ScienceObanScotlandUK National center for Marine Algae and Microbiota Bigelow Laboratory for Ocean SciencesEast BoothbayMEUSA Laboratory of Viral Interactomes GIGA InstituteUniversity of LiegeLiegeBelgium School of Biological Sciences Georgia Institute of TechnologyAtlantaGAUSA

Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity ***,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain *** this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal *** for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular *** genes show phylum-and climate-specific expansions that may facilitate niche ***,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.

关键词： macroalgae multicellularity comparative genomics evolution adhesome endogenous viral elements

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Protocol for the development and validation of a clinical measurement tool for fear of disease progression and recurrence in cardiac patients

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chronic Diseases and Translational Medicine 2024年第3期10卷 195-204页

作者： Sarah T.clarke michael Le Grande Barbara M.Murphy Robert Hester Alun c.Jackson Melbourne School of Psychological Sciences University of MelbourneParkvilleVictoriaAustralia Australian centre for Heart Health MelbourneVictoriaAustralia centre on Behavioral Health University of Hong KongPokfulamHong KongChina

Introduction: One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac ***: The Fear of cardiac Recurrence and Progression Scale (FcRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FcRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric ***: While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FcRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.

关键词： anxiety cardiac anxiety cardiac recovery cardiac rehabilitation depression fear of progression fear of recurrence psychological measurement psychosocial screening

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Stability and Generalization of Hypergraph collaborative Networks

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Machine Intelligence Research 2024年第1期21卷 184-196页

作者： michael K.Ng Hanrui Wu Andy Yip Institute of Data Science The University of Hong KongHong KongChina Department of Mathematics The University of Hong KongHong KongChina college of Information Science and Technology Jinan UniversityGuangzhou 510006China

Graph neural networks have been shown to be very effective in utilizing pairwise relationships across ***,there have been several successful proposals to generalize graph neural networks to hypergraph neural networks to exploit more com-plex *** particular,the hypergraph collaborative networks yield superior results compared to other hypergraph neural net-works for various semi-supervised learning *** collaborative network can provide high quality vertex embeddings and hyperedge embeddings together by formulating them as a joint optimization problem and by using their consistency in reconstructing the given *** this paper,we aim to establish the algorithmic stability of the core layer of the collaborative network and provide generaliz--ation *** analysis sheds light on the design of hypergraph filters in collaborative networks,for instance,how the data and hypergraph filters should be scaled to achieve uniform stability of the learning *** experimental results on real-world datasets are presented to illustrate the theory.

关键词： Hypergraphs vertices hyperedges collaborative networks graph convolutional neural networks(cNNs) stability generalization guarantees

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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie cindy Zhou michael G.Fehlings Division of Genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

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SMXL5 attenuates strigolactone signaling in Arabidopsis thaliana by inhibiting SMXL7 degradation

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Molecular Plant 2024年第4期17卷 631-647页

作者： Qingtian Li Haiyang Yu Wenwen chang Sunhyun chang michael Guzman Lionel Faure Eva-Sophie Wallner Heqin Yan Thomas Greb Lei Wang Ruifeng Yao David c.Nelson Department of Botany and Plant Sciences University of CaliforniaRiversideRiversideCA 2521USA Yazhouwan National Laboratory Sanya 572025China Hainan Seed Industry Laboratory Sanya 57205China State Key Laboratory of chemo/Biosensing and chemometrics Hunan Provincial Key Laboratory of Plant Functional Genomics and Developmental RegulationCollege of BiologyHunan UniversityChangsha 410082China Key Laboratory of Seed Innovation Center for Agricultural Resources ResearchInstitute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangHebei 050021China University of chinese Academy of Sciences Beijing 10004China School of the Sciences Biology DivisionTexas Woman’s UniversityDentonTX 76204USA centre for Organismal Studies(cOS) Heidelberg University6120 HeidelbergGermany

Hormone-activated proteolysis is a recurring theme of plant hormone signaling *** strigolactone signaling,the enzyme receptor DWARF14(D14)and an F-box protein,MORE AXILLARY GROWTH2(MAX2),mark SUPPRESSOR OF MAX21-LIKE(SMXL)family proteins SMXL6,SMXL7,and SMXL8 for rapid *** of these transcriptional corepressors initiates downstream growth *** homologous proteins SMXL3,SMXL4,and SMXL5,however,are resistant to MAX2-mediated *** discovered that the smxl4 smxl5 mutant has enhanced responses to ***5 attenuates strigolactone signaling by interfering with AtD14-SMXL7 ***5 interacts with AtD14 and SMXL7,providing two possible ways to inhibit SMXL7 ***5 function is partially dependent on an ethylene-responsive-element binding-factor-associated amphiphilic repression(EAR)motif,which typically mediates interactions with the TOPLESS family of transcriptional ***,we found that loss of the EAR motif reduces SMXL5-SMXL7 interactions and the attenuation of strigolactone signaling by *** hypothesize that integration of SMXL5 into heteromeric SMXL complexes reduces the susceptibility of SMXL6/7/8 proteins to strigolactone-activated degradation and that the EAR motif promotes the formation or stability of these *** mechanism may provide a way to spatially or temporally fine-tune strigolactone signaling through the regulation of SMXL5 expression or translation.

关键词： Arabidopsis typically inhibiting

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Genetic analyses of ancient tea trees provide insights into the breeding history and dissemination of chinese Assam tea(camellia sinensis ***)

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Plant Diversity 2024年第2期46卷 229-237页

作者： Miao-Miao Li Muditha K.Meegahakumbura Moses c.Wambulwa Kevin S.Burgess michael Möller Zong-Fang Shen De-Zhu Li Lian-Ming Gao cAS Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of ScienceKunming650201China Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of ScienceKunming650201China Kunming college of Life Science University of Chinese Academy of SciencesKunming650201YunnanChina Department of Export Agriculture Faculty of Animal Science and Export AgricultureUva Wellassa UniversityBadulla90000Sri Lanka Department of Life Sciences School of Science and ComputingSouth Eastern Kenya University170-90200KituiKenya Department of Biology Columbus State UniversityUniversity System of GeorgiaColumbusGA31907-5645USA Royal Botanic Garden Edinburgh 20A Inverleith RowEdinburghEH35LRScotlandUK Lijiang Forest Biodiversity National Observation and Research Station Kunming Institute of BotanyChinese Academy of SciencesLijiang674100YunnanChina

chinese Assam tea(camellia sinensis ***)is an important tea crop with a long history of cultivation in Yunnan,*** its potential value as a genetic resource,its genetic diversity and domestication/breeding history remain *** address this issue,we genotyped 469 ancient tea plant trees representing 26 *** *** populations,plus two of its wild relatives(six and three populations of *** and ***,respectively)using 16 nuclear microsatellite *** showed that chinese Assam tea has a relatively high,but comparatively lower gene diversity(H_(S)=0.638)than the wild relative ***(H_S=0.658).clustering in STRUcTURE indicated that chinese Assam tea and its two wild relatives formed distinct genetic groups,with considerable interspecific *** chinese Assam tea accessions clustered into three gene pools,corresponding well with their geographic ***,New Hybrids analysis indicated that 68.48%of ancient chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and Lincang gene *** addition,10%of the ancient chinese Assam tea individuals were found to be hybrids between chinese Assam tea and *** results suggest that chinese Assam tea was domesticated separately in three gene pools(Puer,Lincang and Xishuangbanna)in the Mekong River valley and that the hybrids were subsequently selected during the domestication *** the domestication history of chinese Assam tea in southwestern Yunnan remains complex,our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.

关键词： Tea plant Hybrid origin Genetic diversity Domestication history camellia sinensis var.assamica camellia taliensis

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Low-thermal-budget electrically active thick polysilicon for cMOS-First MEMS-last integration

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MIcROSYSTEMS & NANOENGINEERING 2024年第1期10卷 1-13页

作者： michael, Aron chuang, Ian Yao-Hsiang Kwok, chee Yee Omaki, Kazuo UNSW Sydney NSW 2052 Australia

Low-thermal-budget, electrically active, and thick polysilicon films are necessary for building a microelectromechanical system (MEMS) on top of a complementary metal oxide semiconductor (cMOS). However, the formation of these polysilicon films is a challenge in this field. Herein, for the first time, the development of in situ phosphorus-doped silicon films deposited under ultrahigh-vacuum conditions (similar to 10(-9) Torr) using electron-beam evaporation (UHVEE) is reported. This process results in electrically active, fully crystallized, low-stress, smooth, and thick polysilicon films with low thermal budgets. The crystallographic, mechanical, and electrical properties of phosphorus-doped UHVEE polysilicon films are studied. These films are compared with intrinsic and boron-doped UHVEE silicon films. Raman spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and atomic force microscopy (AFM) are used for crystallographic and surface morphological investigations. Wafer curvature, cantilever deflection profile and resonance frequency measurements are employed to study the mechanical properties of the specimens. Moreover, resistivity measurements are conducted to investigate the electrical properties of the films. Highly vertical, high-aspect-ratio micromachining of UHVEE polysilicon has been developed. A comb-drive structure is designed, simulated, fabricated, and characterized as an actuator and inertial sensor comprising 20-mu m-thick in situ phosphorus-doped UHVEE films at a temperature less than 500 degrees c. The results demonstrate for the first time that UHVEE polysilicon uniquely allows the realization of mechanically and electrically functional MEMS devices with low thermal budgets.

关键词： POLYcRYSTALLINE SILIcON SPUTTERED SILIcON cRYSTALLIZATION TEMPERATURE DEPOSITION FILMS

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng connie chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex c.Haydon Hue H.Luu Sherwin Ho michael J.Lee Jason Strelzow Russell R.Reid Tong-chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-catenin cancer canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Application of a simplified ADM1 for full-scale anaerobic co-digestion of cattle slurry and grass silage:assessment of input variability

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Frontiers of Environmental Science & Engineering 2024年第4期18卷 125-139页

作者： Sofia Tisocco Sören Weinrich Gary Lyons michael Wills Xinmin Zhan Paul crosson civil Engineering College of Science and EngineeringUniversity of GalwayGalwayH91 TK33Ireland Teagasc Animal and Bioscience Research Department Animal and Grassland Research and Innovation CentreDunsanyC15 PW93Ireland Biochemical conversion Department Deutsches Biomasseforschungszentrum gemeinnützige GmbHLeipzig 04347Germany Faculty of Energy·Building Services·Environmental Engineering Münster University of Applied SciencesSteinfurt 48565Germany Agri-Food and Biosciences Institute HillsboroughBT266DRUK Ryan Institute University of GalwayGalwayH91 TK33Ireland MaREI Research centre for Energy Climate and MarineRyan InstituteUniversity of GalwayGalwayH91 TK33Ireland

Mathematical modeling of anaerobic digestion is a powerful tool to predict gas yields and optimize the *** Anaerobic Digestion Model No.1(ADM1)is a widely implemented model for this ***,modeling full-scale biogas plants is challenging due to the extensive substrate and parameter characterization *** study describes the modification of the ADM1 through a simplification of individual process phases,characteristic components and required ***,the ability of the simplified model to simulate the co-digestion of grass silage and cattle slurry was evaluated using data from a full-scale biogas *** impacts of substrate composition(crude carbohydrate,protein and lipid concentration)and variability of carbohydrate degradability on simulation results were assessed to identify the most influential *** indicated that the simplified version was able to depict biogas and biomethane production with average model efficiencies,according to the Nash-Sutcliffe efficiency(NSE)coefficient,of 0.70 and 0.67,respectively,and was comparable to the original ADM1(average model efficiencies of 0.71 and 0.63,respectively).The variability of crude carbohydrate,protein and lipid concentration did not significantly impact biogas and biomethane output for the data sets *** contrast,carbohydrate degradability seemed to explain much more of the variability in the biogas and methane ***,the application of simplified models provides a reliable basis for the process simulation and optimization of full-scale agricultural biogas plants.

关键词： ADM1 Agricultural feedstocks Biogas technology Input variability Parameter estimation

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