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Intracranial arterial four-dimensional flow is associated with metrics of brain health and Alzheimer's disease

Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring 2015年第4期1卷 420-428页

作者： Berman, Sara E. Rivera-Rivera, Leonardo A. Clark, Lindsay R. Racine, Annie M. Keevil, Jon G. Bratzke, Lisa C. Carlsson, Cynthia M. Bendlin, Barbara B. Rowley, Howard A. Blennow, Kaj Zetterberg, Henrik Asthana, Sanjay Turski, Patrick Johnson, Sterling C. Wieben, Oliver Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WI United States Neuroscience Training Program University of Wisconsin-Madison Madison WI United States Medical Scientist Training Program University of Wisconsin-Madison Madison WI United States Department of Medical Physics University of Wisconsin School of Medicine and Public Health Madison WI United States Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health Madison WI United States Department of Radiology University of Wisconsin School of Medicine and Public Health Madison WI United States Department of Medicine University of Wisconsin School of Medicine and Public Health Madison WI United States School of Nursing University of Wisconsin-Madison Madison WI United States Geriatric Research Education and Clinical Center William S. Middleton Memorial Veterans Hospital Madison WI United States Clinical Neurochemistry Laboratory Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden Department of Molecular Neuroscience University College London Institute of Neurology London United Kingdom Waisman Laboratory for Brain Imaging and Behavior University of Wisconsin-Madison Madison WI United States

Introduction: Although cerebrovascular disease has long been known to co-occur with Alzheimer's disease (AD), recent studies suggest an etiologic contribution to AD pathogenesis. We used four dimensional (4D)-flow magnetic resonance imaging (MRI) to evaluate blood flow and pulsatility indices in the circle of Willis. We hypothesized decreased mean blood flow and increased pulsatility, metrics indicative of poor vascular health, would be associated with cerebral atrophy and an AD cerebrospinal fluid (CSF) profile. Methods: A total of 312 patients along the AD continuum (172 middle aged, 60 cognitively healthy older, 44 mild cognitive impairment, and 36 AD) underwent MRI, CSF, and medical examinations. Regression was used to predict CSF biomarkers and atrophy from 4D-flow and analysis of covariance to compare vascular health between groups. Results: Decreased mean flow in the middle cerebral artery (MCA) and superior portion of the internal carotid artery (sICA) and increased pulsatility in the MCA were associated with greater brain atrophy. Decreased mean flow in the sICA was associated with lower amyloid beta 1-42 (Aβ₄₂) in the CSF, a pathologic biomarker profile associated with AD. Interestingly, although metrics of flow and pulsatility differed markedly across the AD spectrum, there were no significant differences in cardiovascular risk score, mean arterial pressure, and pulse pressure across the three age-matched older cohorts. Discussion: By measuring intracranial arterial health directly with 4D-flow MRI, these data suggest that intracranial arterial health is compromised in symptomatic AD. Even after accounting for disease stage, cerebral artery health is associated with atrophy and an AD Aβ₄₂ profile, suggesting neurovascular health may contribute to the etiopathogenesis of AD. © 2015.

关键词： Alzheimer's disease Cardiovascular risk Circle of Willis Mean blood flow Pulsatility index

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Osteolipoma of the knee

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Radiology Case Reports 2017年第1期12卷 124-129页

作者： Huynh, Tien-Phat V. Cipriano, Cara A. Hagemann, Ian S. Friedman, Michael V. Medical Scientist Training Program (MSTP) and Department of Neurology Washington University School of Medicine St. Louis MO United States Department of Orthopedic Surgery Washington University School of Medicine St. Louis MO United States Department of Pathology and Immunology Washington University School of Medicine St. Louis MO United States Department of Radiology Mallinckrodt Institute of Radiology 510 S Kingshighway Blvd St. Louis 63110 MO United States

A case of a right knee intra-articular osteolipoma in a 64-year-old man is reported. The patient presented for evaluation of a 1-year history of nontraumatic, mechanically-exacerbated, medial-sided right knee pain. Radiographs demonstrated a partially calcified 3.0 cm mass anterior to the distal medial femur at the suprapatellar fossa. Magnetic resonance imaging examination confirmed a 4.0 × 3.6 cm well-circumscribed mass deep to the medial patellofemoral ligament, with predominantly fat characteristics on T1-weighted and T2-weighted sequences. The mass had irregular ossification superiorly with surrounding heterogeneous enhancement. Histologic examination of an excisional biopsy showed the lesion to be an osteolipoma. Osteolipoma is a rare histologic variant of lipoma with osseous metaplasia, but should be considered in the differential of a fat-containing neoplasm with ossification. © 2016 The Authors

关键词： Knee joint Ossifying lipoma Osteolipoma

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Brain stem cells as the cell of origin in glioma

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World Journal of Stem Cells 2014年第1期6卷 43-52页

作者： Aram S Modrek N Sumru Bayin Dimitris G Placantonakis Medical Scientist Training Program New York University School of Medicine Department of Neurosurgery New York University School of Medicine Kimmel Center for Stem Cell Biology New York University School of Medicine Brain Tumor Center New York University School of Medicine

Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineagetracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.

关键词： Glioma Cell of origin Cancer stem cells Genetic models Gliomagenesis Neurogenesis

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Stress Relaxation and Composition of Hydrazone-Crosslinked Hybrid Biopolymer-Synthetic Hydrogels Determine Spreading and Secretory Properties of MSCs (Adv. Healthcare Mater. 14/2022)

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ADVANCED HEALTHCARE MATERIALS 2022年第14期11卷 2200393-2200393页

作者： Borelli, Alexandra N. Young, Mark W. Kirkpatrick, Bruce E. Jaeschke, Matthew W. Mellett, Sarah Porter, Seth Blatchley, Michael R. Rao, Varsha V. Sridhar, Balaji V. Anseth, Kristi S. Department of Chemical and Biological Engineering University of Colorado Boulder Boulder CO 80303 USA The BioFrontiers Institute University of Colorado Boulder Boulder CO 80303 USA Medical Scientist Training Program University of Colorado Anschutz Medical Campus Aurora CO 80045 USA Department of Physical Medicine and Rehabilitation University of Colorado Aurora CO 80231 USA

Mesenchymal Stromal Cells Mesenchymal stromal cells (MSCs) are bone-marrow derived stem cells isolated for culture in vitro or in vivo. In article number 2200393 by Kristi S. Anseth and co-workers, MSCs are cultured in vitro, where the red stain, rhodamine phalloidin, visualizes the cell-membrane, and the blue stain, DAPI, visualizes the cell nuclei. This image shows the ability of MSCs to cluster within a stress-relaxing 3D environment.

关键词： hydrogels mesenchymal stromal cells stress relaxation

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RABL6A Promotes Oxaliplatin Resistance in Tumor Cells and Is a New Marker of Survival for Resected Pancreatic Ductal Adenocarcinoma Patients

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Genes and Cancer 2013年第7-8期4卷 273-284页

作者： Muniz, Viviane P. Askeland, Ryan W. Zhang, Xuefeng Reed, Sara M. Tompkins, Van S. Hagen, Jussara McDowell, Bradley D. Button, Anna Smith, Brian J. Weydert, Jamie A. Mezhir, James J. Quelle, Dawn E. The Molecular and Cellular Biology Graduate Program University of Iowa Iowa City IA United States Department of Pathology College of Medicine University of Iowa Iowa City IA United States Department of Pharmacology College of Medicine University of Iowa Iowa City IA United States The Medical Scientist Training Program University of Iowa Iowa City IA United States Holden Comprehensive Cancer Center University of Iowa Iowa City IA United States Department of Biostatistics College of Medicine University of Iowa Iowa City IA United States Department of Surgery College of Medicine University of Iowa Iowa City IA United States

Pancreatic ductal adenocarcinoma (PDAC) is characterized by early recurrence following pancreatectomy, rapid progression, and chemoresistance. Novel prognostic and predictive biomarkers are urgently needed to both stratify patients for clinical trials and select patients for adjuvant therapy regimens. This study sought to determine the biological significance of RABL6A (RAB, member RAS oncogene family-like protein 6 isoform A), a novel pancreatic protein, in PDAC. Analyses of RABL6A protein expression in PDAC specimens from 73 patients who underwent pancreatic resection showed that RABL6A levels are altered in 74% of tumors relative to adjacent benign ductal epithelium. Undetectable RABL6A expression, found in 7% (5/73) of patients, correlated with improved overall survival (range 41 to 118 months with 3/5 patients still living), while patients with RABL6A expression had a worse outcome (range 3.3 to 100 months, median survival 20.3 months) (P = 0.0134). In agreement with those findings, RABL6A expression was increased in pancreatic cancer cell lines compared to normal pancreatic epithelial cells, and its knockdown inhibited pancreatic cancer cell proliferation and induced apoptosis. Moreover, RABL6A depletion selectively sensitized cells to oxaliplatin-induced arrest and death. This work reveals that RABL6A promotes the proliferation, survival, and oxaliplatin resistance of PDAC cells, whereas its loss is associated with extended survival in patients with resected PDAC. Such data suggest RABL6A is a novel biomarker of PDAC and potential target for anticancer therapy. © The Author(s) 2013.

关键词： ARF chemoresistance oxaliplatin pancreatic ductal adenocarcinoma RABL6A

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Leukocyte Isolation from Brain, Spinal Cord, and Meninges for Flow Cytometric Analysis

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Current Protocols in Immunology 2018年第1期121卷 e44-e44页

作者： Manglani, Monica Gossa, Selamawit McGavern, Dorian B. National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda MD United States Medical Scientist Training Program Penn State College of Medicine Hershey United States

A continual dialogue exists between the central nervous system (CNS) and immune system that contributes to neural homeostasis as well as protection from microbes, repair following damage, autoimmune disease, and neurodegeneration. Characterization of resident and peripherally derived leukocyte populations within the central nervous system can provide valuable information regarding how these cells contribute to steady-state and inflammatory conditions. Flow cytometry provides a method to conduct detailed multi-parameter analyses of immune cells isolated from various tissues. This protocol provides a method to isolate leukocytes from brain, spinal cord, and meninges for flow cytometric analysis and provides a basic framework for phenotyping these cells. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

关键词： CNS FACS flow cytometry leukocyte isolation meninges

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Acute myeloid leukemia in elderly patients: New targets, new therapies

Aging and Cancer

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Aging and Cancer 2023年第2期4卷 51-73页

作者： Park, Hae J. Gregory, Mark A. Department of Biochemistry and Molecular Genetics School of Medicine University of Colorado Anschutz Medical Campus Aurora CO United States Medical Scientist Training Program University of Colorado Anschutz Medical Campus Aurora CO United States

Prior to the past few years, the development of new therapies for acute myeloid leukemia (AML) has been disappointingly slow. For several decades, the standard therapy for AML has consisted of intensive induction chemotherapy, and potentially a subsequent hematopoietic stem cell transplant. Unfortunately, older patients are less responsive to, and are frequently unfit to tolerate, such intensive chemotherapy. Given that a majority of AML patients are elderly, this population has been most affected by the lack of newer less toxic therapies. However, in recent years, the treatment landscape for AML has dramatically shifted with the approval of many new drugs. As summarized in this review, several of these new drugs are targeted agents that are better tolerated than standard chemotherapy and could substantially benefit elderly patients. Although drug resistance remains a major concern, the treatment options for elderly AML patients are more numerous than ever before, bringing new promise for improved patient outcomes. © 2023 The Authors. Aging and Cancer published by Wiley Periodicals, Inc.

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Author Correction: Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues

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Nature biotechnology 2025年 2025 May 12页

作者： Lei Chang Yang Xie Brett Taylor Zhaoning Wang Jiachen Sun Ethan J Armand Shreya Mishra Jie Xu Melodi Tastemel Audrey Lie Zane A Gibbs Hannah S Indralingam Tuyet M Tan Rafael Bejar Clark C Chen Frank B Furnari Ming Hu Bing Ren Department of Cellular and Molecular Medicine University of California San Diego La Jolla CA USA. Biomedical Sciences Graduate Program University of California San Diego La Jolla CA USA. Medical Scientist Training Program University of California San Diego La Jolla CA USA. Department of Quantitative Health Sciences Lerner Research Institute Cleveland Clinic Foundation Cleveland OH USA. Systems Biology and Bioinformatics PhD Program Case Western Reserve University School of Medicine Cleveland OH USA. Bioinformatics and Systems Biology Program University of California San Diego La Jolla CA USA. Moores Cancer Center UC San Diego La Jolla CA USA. Department of Neurosurgery University of Minnesota Minneapolis MN USA. Department of Medicine University of California San Diego School of Medicine La Jolla CA USA. Department of Cellular and Molecular Medicine University of California San Diego La Jolla CA USA. biren@health.ucsd.edu. Moores Cancer Center UC San Diego La Jolla CA USA. biren@health.ucsd.edu. Center for Epigenomics Institute for Genomic Medicine School of Medicine University of California San Diego La Jolla CA USA. biren@health.ucsd.edu.

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Engineering and Optimization of Quasi-Nondiffracting Helicon-Like Beams with an Evolutionary Algorithm

IEEE Photonics Journal

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IEEE Photonics Journal 2017年第3期9卷 6101109页

作者： Schroeder, Bryce Zhu, Zhen H. Guo, Changliang Jia, Shu Department of Biomedical Engineering Stony Brook University State University of New York Stony BrookNY11794 United States Medical Scientist Training Program Stony Brook University State University of New York Stony BrookNY11794 United States

Nondiffracting beams maintain their intensity profiles over a large propagation distance without substantial diffraction and exhibit unique propagation trajectories, leading to scientific impacts in various fields. However, the nonlocalized intensity distribution of nondiffracting beams is restrictive for many practical applications. Thus, strategies to optimize the beam profiles remain much in demand. In this report, we demonstrate an evolutionary algorithmic framework for optical beam engineering and optimization and experimentally validate it by realizing quasi-nondiffracting radially self-accelerating (or self-rotating) beams in a high-resolution imaging system. The work reports a tightly confined side-lobe-suppressed helicon-like beam that largely maintains its properties of radial self-acceleration and nondiffraction in the 3-D space. The optimization method represents a new methodological avenue that can be extended to a broad range of beam engineering problems. © 2009-2012 IEEE.

关键词： Fluorescence microscopy

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Suspended Tissue Open Microfluidic Patterning (STOMP)

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Advanced Science 2025年 e2501148页

作者： Haack, Amanda J. Brown, Lauren G. Goldstein, Alex J. Mulimani, Priti Berthier, Jean Viswanathan, Asha R. Kopyeva, Irina Whitten, Jamison M. Lin, Ariel Nguyen, Serena H. Leahy, Thomas P. Bouker, Ella E. Padgett, Ruby M. Mazzawi, Natalie A. Tokihiro, Jodie C. Bretherton, Ross C. Wu, Aaliyah Tapscott, Stephen J. DeForest, Cole A. Popowics, Tracy E. Berthier, Erwin Sniadecki, Nathan J. Theberge, Ashleigh B. Department of Chemistry University of Washington SeattleWA98195 United States Medical Scientist Training Program University of Washington School of Medicine SeattleWA98195 United States Institute for Stem Cell & Regenerative Medicine University of Washington SeattleWA98109 United States Department of Materials Science and Engineering University of Washington SeattleWA98195 United States Department of Laboratory Medicine & Pathology University of Washington SeattleWA98195 United States Oral Health Sciences School of Dentistry University of Washington SeattleWA98195 United States Department of Bioengineering University of Washington SeattleWA98195 United States Molecular Engineering & Sciences Institute University of Washington SeattleWA98109 United States Department of Mechanical Engineering University of Washington SeattleWA98195 United States Department of Microbiology University of Washington SeattleWA98195 United States Human Biology Division Fred Hutchinson Cancer Center SeattleWA98109 United States Department of Neurology University of Washington SeattleWA98195 United States Department of Chemical Engineering University of Washington SeattleWA98195 United States Institute for Protein Design University of Washington SeattleWA98195 United States Department of Urology University of Washington School of Medicine SeattleWA98195 United States

Free-standing tissue structures tethered between pillars are powerful mechanobiology tools for studying cell contraction. To model interfaces ubiquitous in natural tissues and upgrade existing single-region suspended constructs, we developed Suspended Tissue Open Microfluidic Patterning (STOMP), a method to create multi-regional suspended tissues. STOMP uses open microfluidics and capillary pinning to pattern subregions within free-standing tissues, facilitating the study of complex tissue interfaces, such as diseased-healthy boundaries (e.g., fibrotic-healthy) and tissue-type interfaces (e.g., bone-ligament). We observed altered contractile dynamics in fibrotic-healthy engineered heart tissues compared to single-region tissues and differing contractility in bone-ligament enthesis constructs compared to single-tissue periodontal ligament models. STOMP is a versatile platform – surface tension-driven patterning removes material requirements common with other patterning methods (e.g., shear-thinning, photopolymerizable) allowing tissue generation in multiple geometries with native extracellular matrices and advanced four-dimensional (4D)- materials. STOMP combines the contractile functionality of suspended tissues with precise patterning, enabling dynamic and spatially controlled studies. © 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH.

关键词： Scaffolds (biology)

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