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作者： Nelson, Andrew W. Knight, Andrew W. May, Dustin Eitrheim, Eric S. Schultz, Michael K. Interdisciplinary Human Toxicology Program University of Iowa Iowa CityIA52242 United States Department of Chemistry University of Iowa Iowa CityIA52242 United States State Hygienic Laboratory University of Iowa CoralvilleIA52241 United States Department of Radiology Medical Scientist Training Program University of Iowa 500 Newton Road ML B180 FRRB Iowa CityIA52242 United States

ISBN: (纸本)9780841231221

As unconventional drilling has emerged as a major industry in the U.S. and around the world, many environmental health and pollution risks have surfaced. One emerging concern is the risk of environmental contamination arising from unconventional wastes that are enriched in naturally-occurring radioactive materials (NORM). Although NORM has been a well-documented contaminant of oil and gas wastes for decades, there are new challenges associated with unconventional drilling. This chapter will present the origin of NORM in black shale formations. In addition, we present the fundamentals of radioactive decay and ingrowth, so as to provide a foundation for a discussion of the potential for environmental impact of NORM. Finally, within this context, we highlight key-relatively-unexplored aspects of unconventional drilling that point to the need for further environmental radiochemistry research. © 2015 American Chemical Society.

关键词： Health risks

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Ubiquitin and the DNA double-strand break repair pathway

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Genome Instability & Disease 2019年第2期1卷 69-80页

作者： Somaira Nowsheen Min Deng Zhenkun Lou Mayo Clinic Medical Scientist Training Program Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences Mayo Clinic Rochester USA Division of Oncology Mayo Clinic Rochester USA

The ubiquitin system plays a central role in diverse cellular processes including DNA damage response. As such, it is not surprising that its dysfunction contributes to various diseases including cancer and neurodegenerative disorders. An understanding of the ubiquitin system is, therefore, important in devising treatments for such diseases. In this review, we discuss the central role of ubiquitin in DNA damage response, specifically DNA double-strand break repair. We focus on recent findings on the role of ubiquitin in the DNA double-strand break repair pathway, possible nodes of modulation, and finally their implications for treatment of various diseases.

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Prefrontal cortical alterations of glutamate and GABA neurotransmission in schizophrenia: Insights for rational biomarker development

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Biomarkers in Neuropsychiatry 2020年 3卷 100015-100015页

作者： Schoonover, Kirsten E. Dienel, Samuel J. Lewis, David A. Translational Neuroscience Program Department of Psychiatry School of Medicine University of Pittsburgh United States Medical Scientist Training Program University of Pittsburgh United States Department of Neuroscience Dietrich School of Arts and Sciences University of Pittsburgh United States Center for the Neural Basis of Cognition Carnegie Mellon University United States

Certain cognitive deficits in schizophrenia, such as impaired working memory, are thought to reflect alterations in the neural circuitry of the dorsolateral prefrontal cortex (DLPFC). Gamma oscillations in the DLPFC appear to be a neural corollary of working memory function, and the power of these oscillations during working memory tasks is lower in individuals with schizophrenia. Thus, gamma oscillations represent a potentially useful biomarker to index dysfunction in the DLPFC circuitry responsible for working memory in schizophrenia. Postmortem studies, by identifying the cellular basis of DLPFC dysfunction, can help inform the utility of biomarker measures obtained in vivo. Given that gamma oscillations reflect network activity of excitatory pyramidal neurons and inhibitory GABA neurons, we review postmortem findings of alterations to both cell types in the DLPFC and discuss how these findings might inform future biomarker development and use. © 2020 The Author(s)

关键词： Cognition GABA gamma oscillations Glutamate Schizophrenia Working memory

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A broad antibody with enhanced HIV-1 neutralization via bispecific antibody-mediated prepositioning

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Nature Communications 2025年第1期16卷 1-14页

作者： Kim, Soohyun Radford, Caelan E. Xu, Duo Zhong, Jianing Do, Jonathan Pham, Dominic M. Travisano, Katie A. Filsinger Interrante, Maria V. Bruun, Theodora U. J. Rezek, Valerie Wilder, Bailey Palomares, Martina Seaman, Michael S. Kitchen, Scott G. Bloom, Jesse D. Kim, Peter S. Department of Biochemistry Stanford University School of Medicine Stanford CA United States Sarafan ChEM-H Stanford University Stanford CA United States Molecular and Cellular Biology Graduate Program University of Washington and Basic Sciences Division Fred Hutchinson Cancer Center Seattle WA United States Basic Sciences Division and Computational Biology Program Fred Hutchinson Cancer Center Seattle WA United States Department of Chemistry Stanford University Stanford CA United States Stanford Biophysics Program Stanford University School of Medicine Stanford CA United States Department of Microbiology & Immunology Stanford University School of Medicine Stanford CA United States Stanford Medical Scientist Training Program Stanford University School of Medicine Stanford CA United States Department of Medicine Division of Hematology and Oncology David Geffen School of Medicine at University of California Los Angeles (UCLA) Los Angeles CA United States UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research David Geffen School of Medicine University of California Los Angeles (UCLA) Los Angeles CA United States Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School Boston MA United States Howard Hughes Medical Institute Seattle WA United States Chan Zuckerberg Biohub San Francisco CA United States Department of Biochemistry University of Wisconsin-Madison Madison WI United States

Antibodies targeting the highly conserved prehairpin intermediate (PHI) of class I viral membrane-fusion proteins are generally weakly neutralizing and are not considered viable therapeutic agents. We previously demonstrated that antibodies targeting the gp41 N-heptad repeat (NHR), which is transiently exposed in the HIV-1 PHI, exhibit enhanced broad neutralization in cells expressing the Fc receptor, FcγRI. To enhance neutralization in cells lacking FcγRI, we here develop a bispecific antibody (bsAb) by fusing an NHR-targeting antibody to an antibody against CD4, the HIV-1 receptor on T cells. The bsAb provides a 5000-fold neutralization enhancement and shows unprecedented neutralization breadth compared to existing broadly neutralizing antibodies. Importantly, the bsAb reduces viral load in HIV-1-infected humanized male mice, and viral envelope sequencing under bsAb pressure revealed an NHR mutation that potentially impairs viral fitness. These findings validate the NHR as a potential HIV-1 therapeutic target, setting the stage for a new class of broadly neutralizing antibodies. © The Author(s) 2025.

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Common AAV gene therapy vectors show nonselective transduction of ex vivo human brain tissue

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Molecular Therapy Methods & Clinical Development 2025年第2期33卷

作者： JP McGinnis Joshua Ortiz-Guzman Maria Camila Guevara Sai Mallannagari Benjamin D.W. Belfort Suyang Bao Snigdha Srivastava Maria Morkas Emily Ji Angela Addison Evelyne K. Tantry Sarah Chen Ying Wang Zihong Chen Kalman A. Katlowitz Jeffrey J. Lange Melissa M. Blessing Carrie A. Mohila M. Cecilia Ljungberg Guillermo Aldave Benjamin R. Arenkiel Department of Neurosurgery Baylor College of Medicine Houston TX 77030 USA Jan and Dan Duncan Neurological Research Institute Texas Children’s Hospital Houston TX 77030 USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX 77030 USA Medical Scientist Training Program Baylor College of Medicine Houston TX 77030 USA Development Disease Models & Therapeutics Graduate Program Baylor College of Medicine Houston TX 77030 USA Stowers Institute for Medical Research Kansas City MO 64110 USA Department of Pathology Texas Children’s Hospital Baylor College of Medicine Houston TX 77030 USA Department of Pediatrics Texas Children’s Hospital Baylor College of Medicine Houston TX 77030 USA Department of Neurosurgery Texas Children’s Hospital Baylor College of Medicine Houston TX 77030 USA

The ability to deliver a therapeutic sequence to a specific cell type in the human brain would make possible innumerable therapeutic options for some of our most challenging diseases; however, studies on adeno-associated virus (AAV) vector tropism have generally relied on animal models with limited translational utility. For this reason, establishing the tropism of common adeno-associated virus (AAV) vectors in living human brain tissue serves as an important baseline for further optimization, as well as a determination of human brain cell types transduced by clinically approved gene therapy vectors AAV2 and AAV9. We have adapted an ex vivo organotypic model to evaluate AAV transduction properties in living slices of human brain tissue. Using fluorescent reporter expression and single-nucleus RNA sequencing, we found that common AAV vectors show broad transduction of normal cell types, with protein expression most apparent in astrocytes; this work introduces a pipeline for identifying and optimizing AAV gene therapy vectors in human brain samples.

关键词： gene therapy human brain AAV AAV tropism human brain organotypic slice culture

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Heart Block Caused by Cardiac Metastasis From Merkel Cell Carcinoma: A Case Report

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Mayo Clinic Proceedings: Innovations, Quality and Outcomes 2019年第4期3卷 510-516页

作者： Kazemi, Nazanin Yeganeh Jain, Christopher Bois, Melanie C. Behfar, Atta Olivier, Kenneth Markovic, Svetomir N. Medical Scientist Training Program Mayo Clinic Rochester MN United States Department of Cardiovascular Medicine Mayo Clinic Rochester MN United States Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States Department of Radiation Oncology Mayo Clinic Rochester MN United States Department of Oncology Mayo Clinic Rochester MN United States

Merkel cell carcinoma (MCC) is a rare, rapidly proliferating skin cancer that commonly metastasizes to regional lymph nodes. We present the case of a 73-year-old woman with a history of MCC and non-Hodgkin B-cell lymphoma who presented with second-degree heart block (Mobitz type II) caused by an interatrial mass. Temporary pacing was required before biopsy, which revealed metastatic MCC. Treatment included permanent pacing, anti–programmed cell death ligand 1 immunotherapy, and radiation to the heart resulting in notable decrease in tumor size and normalized cardiac rhythm. © 2019 Mayo Foundation for medical Education and Research

关键词： CM, cardiac metastases CT, computed tomography FDG, [18F]-fluorodeoxyglucose MCC, Merkel cell carcinoma MCPyV, Merkel cell polyomavirus MRI, magnetic resonance imaging PD-L1, programmed cell death ligand 1 PET, positron emission tomography

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Glioblastoma stem cells:Molecular characteristics and therapeutic implications

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World Journal of Stem Cells 2014年第2期6卷 230-238页

作者： Nermin Sumru Bayin Aram Sandaldjian Modrek Dimitris George Placantonakis Department of Neurosurgery New York University School of Medicine Stem Cell Biology Training Program New York University School of Medicine Medical Scientist Training Program 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

Glioblastoma Multiforme(GBM)is a grade IV astrocytoma,with a median survival of 14.6 *** GBM,stem-like cells,namely glioblastoma stem cells(GSCs),have the ability to self-renew,differentiate into distinct lineages within the tumor and initiate tumor xenografts in immunocompromised animal *** importantly,GSCs utilize cell-autonomous and tumor microenvironment-mediated mechanisms to overcome current therapeutic *** are,therefore,very important therapeutic *** the functional criteria defining GSCs are well defined,their molecular characteristics,the mechanisms whereby they establish the cellular hierarchy within tumors,and their contribution to tumor heterogeneity are not well *** review is aimed at summarizing current findings about GSCs and their therapeutic importance from a molecular and cellular point of view.A better characterization of GSCs is crucial for designing effective GSCtargeted therapies.

关键词： Glioblastoma Glioblastoma stem cells Selfrenewal Differentiation Molecular markers Therapy resistance

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Bilateral pseudo-internuclear ophthalmoplegia in a patient with myasthenia gravis

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American Journal of Ophthalmology Case Reports 2018年 12卷 76-78页

作者： McClard, Cynthia K. Lyons, Lance J. Yalamanchili, Sushma School of Medicine Baylor College of Medicine Houston TX United States School of Medicine Baylor College of Medicine Medical Scientist Training Program Houston TX United States Department of Ophthalmology UTMB Galveston TX United States Department of Ophthalmology Methodist Eye Associates Blanton Eye Institute Houston Methodist Hospital Houston TX United States

Purpose: To report a case of myasthenia gravis presenting with a false localizing sign, a bilateral pseudo internuclear ophthalmoplegia. Observations: A 61 year-old male presented with a five-week history of painless binocular oblique diplopia that was associated with fatigue, vocal hoarseness and bilateral ptosis, the latter two of which worsened through the course of the day. Exam was remarkable for an apparent bilateral internuclear ophthalmoplegia (INO). MRI of the brain with and without contrast and MRA of the head and neck were within normal limits. Lab work was positive for anti-AChR binding, blocking, and modulating antibodies, as well as anti-striated muscle and anti-titin antibodies. The patient was initiated on therapy for myasthenia gravis. Conclusion and importance: Although myasthenia gravis often presents with ptosis or diplopia, rarely patients may develop pseudo-INO secondary to extraocular muscle weakness. True INO occurs with damage to the medial longitudinal fasciculus, a myelinated tract of fibers that controls yoked horizontal eye movements. Clinicians should be suspicious of the false localizing sign of a pseudo-INO associated with myasthenia gravis when more common causes of INO have been excluded. © 2018

关键词： False localizing signs Myasthenia gravis Ocular myasthenia gravis Pseudo internuclear ophthalmoplegia

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Melanoma in a patient with previously unrecognized Birt-Hogg-Dubé syndrome

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JAAD Case Reports 2019年第11期5卷 947-952页

作者： Nowsheen, Somaira Hand, Jennifer L. Gibson, Lawrence E. el-Azhary, Rokea A. Mayo Clinic Medical Scientist Training Program Mayo Clinic Rochester MN United States Department of Dermatology Mayo Clinic Rochester MN United States Department of Pediatrics and Adolescent Medicine Mayo Clinic Rochester MN United States Department of Clinical Genomics Mayo Clinic Rochester MN United States Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States

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Reinforcement Learning for Control of Evolutionary and Ecological Processes

arXiv

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arXiv 2023年

作者： Bagley, Bryce Allen Khoshnan, Navin Petritsch, Claudia K. Mathematical Medicine Group Stanford University United States Petritsch Laboratory Department of Neurosurgery Stanford Medical School United States Physician-Scientist Training Program Stanford Medical School United States

As Evolutionary Dynamics moves from the realm of theory into application, algorithms are needed to move beyond simple models. Yet few such methods exist in the literature. Ecological and physiological factors are known to be central to evolution in realistic contexts, but accounting for them generally renders problems intractable to existing methods. We introduce a formulation of evolutionary games which accounts for ecology and physiology by modeling both as computations and use this to analyze the problem of directed evolution via methods from Reinforcement Learning. This combination enables us to develop first-of-their-kind results on the algorithmic problem of learning to control an evolving population of cells. We prove a complexity bound on eco-evolutionary control in situations with limited prior knowledge of cellular physiology or ecology, give the first results on the most general version of the mathematical problem of directed evolution, and establish a new link between AI and *** Codes 93 (Primary) 68Txx, 92Dxx, 92Cxx (Secondary) © 2023, CC BY-NC-ND.

关键词： Anthropogenic

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