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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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NEcAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Schafer Sudena Wang michael J.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NEcAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized c-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NEcAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NEcAB2 interacts with predominantly striatal G-protein-coupled receptors, while NEcAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NEcAB proteins exhibit distinct subcellular localizations: NEcAB1 is found in the nucleus and cytosol, NEcAB2 resides in endosomes and the plasma membrane, and NEcAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NEcAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NEcAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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PARALLEL HIERARcHIcAL MATRIX PREcONDITIONERS FOR THE cURL-cURL OPERATOR

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Journal of computational Mathematics 2009年第5期27卷 624-641页

作者： Mario Bebendorf Joerg ostrowski Institut fur Numerische Simulation Universitat BonnWegelerstrasse 653115 BonnGermany ABB Switzerland Ltd Corporate ResearchSegelhofstrasse 1 K/P.O.BoxCH-5405 Baden 5 Dattwil

This paper deals with the preconditioning of the curl-curl operator. We use H（curl）- conforming finite elements for the discretization of our corresponding magnetostatic model problem. Jumps in the material parameters influence the condition of the problem. We will demonstrate by theoretical estimates and numerical experiments that hierarchical matrices are well suited to construct efficient parallel preconditioners for the fast and robust iterative solution of such problems.

关键词： computational electromagnetism Preconditioners Hierarchical matrices Parallelization.

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Electronic warfare in the optical band:Main features,examples and selected measurement data

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Defence Technology（防务技术） 2021年第5期17卷 1636-1649页

作者： Roman ostrowski Artur cywinski Marek Strzelec Polish Naval Academy Navigation and Naval Weapons Faculty69Smidowicza Str.81-127GdyniaPoland Military University of Technology Institute of Optoelectronics2 Gen.S.Kaliskiego Str.00-908WarsawPoland

The paper presents the possibilities of,and methods for,acquiring,analysing and processing optical signals in order to recognise,identify and counteract threats on the contemporary *** main ways electronic warfare is waged in the optical band of the electromagnetic wave spectrum have been formulated,including the acquisition of optical emitter signatures,as well as ultraviolet(UV)and thermal(IR)*** physical parameters and values describing the emission of laser radiation are discussed,including their importance in terms of creating optical ***,it has been shown that in the transformation of optical signals into signatures,only their spectral and temporal parameters can be *** was confirmed in experimental part of the paper,which includes our own measurements of spectral and temporal emission characteristics for three types of binocular laser *** has been further shown that through simple registration and quick analysis involving comparison of emission time parameters in the case of UV signatures in“solar-blind”band,various events can be identified quickly and *** same is true for IR signatures,where the amplitudes of the recorded signal for several wavelengths are *** was confirmed experimentally for UV signatures by registering and then analyzing signals from several events during military exercises at a training ground,namely Rocket Propelled Grenade(RPG)launches and explosions after hitting targets,trinitrotoluene(TNT)explosions,firing armour-piercing,fin-stabilised,discarding sabots(APFSDS)or high explosive(HE)*** final section describes a proposed model database of emitters,created as a result of analysing and transforming the recorded signals into optical signatures.

关键词： Optoelectronics Electronic warfare Optical signature

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Hepatocellular carcinoma recurrence after liver transplant:An Australian single-centre study

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World Journal of Transplantation 2025年第1期15卷 105-114页

作者： Matthew G Garas Luis calzadilla-Bertot Briohny W Smith Luc Delriviere Byron Jaques Lingjun Mou Leon A Adams Gerry c MacQuillan George Garas Gary P Jeffrey michael c Wallace Medical School University of Western AustraliaNedlands 6009Western AustraliaAustralia Department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Department of Surgery Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia

BAcKGROUND Hepatocellular carcinoma(Hcc)is a leading cause of cancer-related deaths *** transplantation(LT)offers the most effective *** recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for *** rate of Hcc recurrence is generally reported as 8%-20%in the *** predictors of Hcc have already been researched,however,to our knowledge there are no published studies on this topic using Australian *** To determine the rate and identify predictors of Hcc recurrence in a contemporary Western Australian LT *** We performed a retrospective cohort study of all liver transplants in patients with Hcc at Sir charles Gairdner Hospital between 2006 and *** was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of *** survival of Hcc patients post-LT,stratified for recurrence,was calculated by Kaplan Meier *** and multivariate cox regression was used to determine predictors of Hcc recurrence *** Between 1/1/2006 and 12/31/2021,119 patients were transplanted with Hcc.8.4%of subjects developed recurrent Hcc after LT with median follow-up time of 5.4 *** median time to recurrence was 2.9 years±0.75 *** comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated Hcc(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with Hcc recurrence compared to those without Hcc recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank PcONcLUSION Hcc recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT *** studies are requir

关键词： Liver cancer Recurrence Liver transplantation Hepatocellular carcinoma Predictors Post-transplant survival Australian data

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controversies in fecal incontinence

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World Journal of Gastroenterology 2025年第3期31卷 113-119页

作者： Andreia Albuquerque Satish S c Rao School of Medicine and Biomedical Sciences Fernando Pessoa UniversityGondomar 4420-096PortoPortugal Precancerous Lesions and Early cancer Management Research Group RISE@cI-IPO(Health Research Network) Portuguese Oncology Institute of PortoPorto 4200-072Portugal Division of Gastroenterology and Hepatology Department of Internal MedicineAugusta UniversityAugustaGA 30912United States

Fecal incontinence is a common condition that can significantly impact patients’quality of *** anal sphincter injury and anorectal surgeries are common *** ultrasound and anorectal manometry are important diagnostic tools for evaluating *** are various treatment options,including diet,lifestyle modifications,drugs,biofeedback therapy,tibial and sacral nerve neuromodulation therapy,and *** this editorial,we will discuss current controversies and novel approaches to fecal *** for asymptomatic anal sphincter defects after obstetric anal sphincter injury and in patients with inflammatory bowel disease is not generally recommended,but may be helpful in selected *** Garg incontinence score is a new score that includes the assessment of solid,liquid,flatus,mucous,stress and urge fecal *** tests such as translumbosacral anorectal magnetic stimulation and novel therapies such as translumbosacral neuromodulation therapy are promising diagnostic and treatment options,for both fecal incontinence and *** biofeedback therapy can overcome some limitations of the office-based *** muscle-derived cell implantation of the external anal sphincter has been further studied as a possible treatment *** neuromodulation may be useful in scleroderma,congenital fecal incontinence and inflammatory bowel disease but merits further study.

关键词： Fecal incontinence Endoanal ultrasound Anal sphincter defects Biofeedback Neuropathy Sacral neuromodulation

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Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru c.Guo Division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada Division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada Faculty of Medicine–The University of British columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science core collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P Gc-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

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Systematic Assessment of Synthesized Tri-magnesium Phosphate Powders(Amorphous,Semi-crystalline and crystalline) and cements for ceramic Bone cement Applications

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Journal of Materials Science & Technology 2015年第5期31卷 437-444页

作者： Nicole ostrowski Vidisha Sharma Abhijit Roy Prashant N.Kumta Department of Bioengineering University of Pittsburgh center of complex Engineered Multifunctional Materials University of Pittsburgh Department of chemical and Petroleum Engineering University of Pittsburgh Department of Mechanical Engineering and Materials Science University of Pittsburgh

Magnesium phosphate cements have come under investigation in recent years for use as an alternative to calcium phosphate cements for bone void repair *** indicates that magnesium phosphate cements obtain higher initial strengths after cement reaction and resorption in more clinically appropriate time frames than commercially available calcium phosphate *** this study,amorphous,partially amorphous and crystalline tri-magnesium phosphate powders were synthesized via an aqueous precipitation reaction with subsequent thermal treatment,and characterized using techniques such as X-ray diffraction and Fourier transform infrared *** materials were assessed for their functionality in cementing reaction with a 3.0 mol/L,pH 7.0 ammonium phosphate solution,including setting time and pH evolution in phosphate buffered saline *** indicated that the amorphous and semi-crystalline tri-magnesium phosphate powders were highly reactive with the setting solution but resulted in mechanically weak cements,while the crystalline tri-magnesium phosphate powder reacted efficiently with the cement solution and were mechanically strong following the cement reaction.X-ray diffraction and scanning electron microscopy analyses indicated significant changes in the phase composition and morphology of the cements following incubation in phosphate buffered *** were perceived to be detrimental to the integrity of the amorphous and semi-crystalline tri-magnesium phosphate derived cements but not to those created with fully crystalline tri-magnesium *** crystalline tri-magnesium phosphate material resulted in the most functional cement as this embodiment displayed the most clinically relevant setting time as well as the highest mechanical resilience and neutral pH during incubation in saline solution rendering them potentially viable as bone void fillers.

关键词： Amorphous magnesium phosphate Tri-magnesium phosph

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Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon c.Smith Jessica L.Williams Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(cNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

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A framework for computer vision-based health monitoring of a truss structure subjected to unknown excitations

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Earthquake Engineering and Engineering Vibration 2023年第1期22卷 1-17页

作者： Mariusz ostrowski Bartlomiej Blachowski Bartosz Wójcik Mateusz Żarski Piotr Tauzowski Łukasz Jankowski Institute of Fundamental Technological Research Polish Academy of SciencesWarsawPoland Silesian University of Technology GliwicePoland Institute of Theoretical and Applied Informatics Polish Academy of SciencesGliwicePoland

computer vision(cV)methods for measurement of structural vibration are less expensive,and their application is more straightforward than methods based on sensors that measure physical quantities at particular points of a ***,cV methods produce significantly more measurement ***,computer vision-based structural health monitoring(cVSHM)requires appropriate methods of damage assessment that are robust with respect to highly contaminated measurement *** this paper a complete cVSHM framework is proposed,and three damage assessment methods are *** first is the augmented inverse estimate(AIE),proposed by Peng et *** *** method is designed to work with highly contaminated measurement data,but it fails with a large noise provided by cV *** second method,as proposed in this paper,is based on the AIE,but it introduces a weighting matrix that enhances the conditioning of the *** third method,also proposed in this paper,introduces additional constraints in the optimization process;these constraints ensure that the stiffness of structural elements can only *** proposed methods perform better than the original *** latter of the two proposed methods gives the best results,and it is robust with respect to the selected coefficients,as required by the algorithm.

关键词： computer vision structural health monitoring physics-based graphical models augmented inverse estimate model updating non-negative least square method

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