Article
Biochemistry & Molecular Biology
Tierra A. Bobo, Preston N. Samowitz, Michael Robinson, Laura Montes, Lawrence J. Forsberg, Richard Feng, Nathan Nicely, Haiyan Fu
Summary: The presence of pre-existing alpha AAV-Abs in humans poses a challenge in the translation of AAV gene therapy. This study developed a modified version of the IgG degrading enzyme (IdeS) that can specifically cleave IgG in humans and rabbits. In animal models, IdeS showed promising results in depleting pre-existing alpha AAV-Abs, allowing for effective gene therapy.
Article
Biotechnology & Applied Microbiology
Hideto Morimoto, Sachiho Kida, Eiji Yoden, Masafumi Kinoshita, Noboru Tanaka, Ryuji Yamamoto, Yuri Koshimura, Haruna Takagi, Kenichi Takahashi, Tohru Hirato, Kohtaro Minami, Hiroyuki Sonoda
Summary: This study demonstrated that a BBB-penetrable antibody-enzyme fusion protein pabinafusp alfa can prevent neurodegeneration and neurocognitive dysfunction in MPS II mice by reducing heparan sulfate deposition in the brain. The correlation between HS concentrations in the brain and cerebrospinal fluid suggests that maintenance of neurocognitive function can be predicted from CSF.
Article
Immunology
Hai Duc Nguyen, Won Hee Jo, Ngoc Hong Minh Hoang, Min -Sun Kim
Summary: Cognitive impairment and organic solvent exposure are significant concerns in public health. This study investigated the therapeutic effects of risperidone on cognitive impairment caused by 1,2-diacetylbenzene (DAB) using in vivo and in silico methods. Risperidone was found to alleviate DAB-induced cognitive impairment through various molecular mechanisms, including inhibition of GSK-3β, amyloid-β, CDK5, BACE, and tau hyperphosphorylation. It also suppressed DAB-induced activation of inflammatory pathways and oxidative stress. In silico analyses identified the involvement of prolactin signaling, miRNA regulation, and CEBPB in the pathophysiology of DAB-induced cognitive impairment. These findings suggest the potential use of risperidone in treating cognitive impairment caused by organic solvents, particularly DAB.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Pengpeng Liu, Shun-Qing Liang, Chunwei Zheng, Esther Mintzer, Yan G. Zhao, Karthikeyan Ponnienselvan, Aamir Mir, Erik J. Sontheimer, Guangping Gao, Terence R. Flotte, Scot A. Wolfe, Wen Xue
Summary: The study introduces an NLS-optimized SpCas9-based prime editor that enhances genome editing efficiency and demonstrates the potential to induce tumor formation and correct pathogenic mutations in adult mice through somatic cell editing. The use of dual adeno-associated virus (AAVs) for delivery of a split-intein prime editor further establishes the capability of this system for in vivo installation of sequence modifications with important implications for disease modeling and correction.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Lidia Castillo-Mariqueo, M. Jose Perez-Garcia, Lydia Gimenez-Llort
Summary: The study on the 3xTg-AD mouse model reveals significant functional impairments in gait and exploratory activity in patients with Alzheimer's disease, which worsen with disease severity and aging. This indicates the potential for using the ICF framework in rehabilitation and understanding of functional decline in AD patients.
Article
Biochemistry & Molecular Biology
Jenna Magat, Samantha Jones, Brian Baridon, Vishal Agrawal, Hio Wong, Alexander Giaramita, Linley Mangini, Britta Handyside, Catherine Vitelli, Monica Parker, Natasha Yeung, Yu Zhou, Erno Pungor, Ilya Slabodkin, Olivia Gorostiza, Allora Aguilera, Melanie J. Lo, Saida Alcozie, Terri M. Christianson, Pascale M. N. Tiger, Jon Vincelette, Sylvia Fong, Geuncheol Gil, Chuck Hague, Roger Lawrence, Daniel J. Wendt, Jonathan H. Lebowitz, Stuart Bunting, Sherry Bullens, Brett E. Crawford, Sushmita M. Roy, Josh C. Woloszynek
Summary: This study demonstrates the efficacy of rhSGSH in treating MPS IIIA through intracerebroventricular delivery. RhSGSH can completely normalize lysosomal HS storage and markers of neuroimmune response.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Yu-Xin Ding, Gao-Wa Eerduna, Si-Jin Duan, Ting Li, Rong-Xia Liu, Lei-Ming Zhang, Tian Wang, Feng-Hua Fu
Summary: The study demonstrates that escin improves neurological function in ICH mice by ameliorating systemic inflammation instead of directly targeting the brain, notably by inhibiting the IL-1 beta/RhoA/NF-kappa B signaling pathway in the blood-brain barrier. This suggests a potential therapeutic approach for brain injury post-ICH.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Immunology
Rui Tada, Haruka Yamazaki, Yuzuho Nagai, Yukino Takeda, Akihiro Ohshima, Jun Kunisawa, Yoichi Negishi
Summary: The COVID-19 pandemic caused by the highly virulent SARS-CoV-2 has had a significant impact on global society. Mucosal vaccines, which can induce immune responses at both mucosal and systemic sites, could be a potential approach to combat infectious diseases. This study demonstrated that intranasal administration of the nitric oxide donor SNP had potent mucosal adjuvant effects in mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biology
Jamie L. Courtland, Tyler W. A. Bradshaw, Greg Waitt, Erik J. Soderblom, Tricia Ho, Anna Rajab, Ricardo Vancini, Il Hwan Kim, Scott H. Soderling
Summary: Mutation of SWIP destabilizes the WASH complex, leading to disruptions in endosomal and lysosomal pathways, and resulting in neurodegeneration and motor deficits. These findings support a model where cognitive and motor impairments are driven by endo-lysosomal dysfunction in the brain due to WASH complex destabilization caused by SWIPP1019R.
Article
Neurosciences
Chengyun Cai, Lifeng Wang, Shixin Li, Shengchun Lou, Jia-lie Luo, Ding-Yi Fu, Tingting Chen
Summary: This study found that lonafarnib can improve the synaptic structure and function in Alzheimer's disease (AD) mice, leading to improved spatial cognition. This improvement may be related to lonafarnib increasing the levels of brain-derived neurotrophic factor (BDNF) through the H-Ras-alpha 7nAChR-dependent CaMKII-CREB pathway.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Yasuhiro Ikabata, Hiromi Nakai
Summary: This paper discusses relativistic quantum chemical calculations based on the Dirac picture and the Schrodinger picture, focusing on the importance of the picture-change effect and picture-change correction. The electron density is a fundamental variable in relativistic density functional theory, making the implementation of picture-change correction essential for numerical agreement and fundamental theory perspective.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Pharmacology & Pharmacy
Johanna Walther, Danny Wilbie, Vincent S. J. Tissingh, Mert Oktem, Heleen van der Veen, Bo Lou, Enrico Mastrobattista
Summary: In this study, we optimized the formulation conditions of lipid nanoparticles (LNP) for efficient delivery of CRISPR-Cas9 components. We found that low concentrations of certain components were necessary for gene correction, while specific components were not required for gene knock-out. Additionally, we discovered that LNP interacted with plasma but remained stable, with HDR template favoring stability.
Article
Neurosciences
Christiaan F. M. Huffels, Roland E. van Dijk, Henk Karst, Frank J. Meye, Elly M. Hol, Jinte Middeldorp
Summary: The study demonstrates that blood-borne factors are sufficient to drive neurophysiological impairments in the hippocampal CA1, leading to impaired levels of long-term potentiation (LTP). These impairments are similar to those found in mouse models for AD.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Nanoscience & Nanotechnology
Fen Qiu, Long Xi, Shengshuang Chen, Yonghua Zhao, Zhenping Wang, Ying Zheng
Summary: Cel Nio gel achieved the anti-psoriatic effect by inhibiting inflammation and hyperproliferation of keratinocytes in the skin, further suppressing systemic inflammation. The gel demonstrated significant local and systemic therapeutic effects in treating psoriasis.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Multidisciplinary Sciences
Xinhong Chen, Damien A. Wolfe, Dhanesh Sivadasan Bindu, Mengying Zhang, Naz Taskin, David Goertsen, Timothy F. Shay, Erin E. Sullivan, Sheng-Fu Huang, Sripriya Ravindra Kumar, Cynthia M. Arokiaraj, Viktor M. Plattner, Lillian J. Campos, John K. Mich, Deja Monet, Victoria Ngo, Xiaozhe Ding, Victoria Omstead, Natalie Weed, Yeme Bishaw, Bryan B. Gore, Ed S. Lein, Athena Akrami, Cory Miller, Boaz P. Levi, Annika Keller, Jonathan T. Ting, Andrew S. Fox, Cagla Eroglu, Viviana Gradinaru
Summary: Efficiently and specifically delivering genes across the brain vasculature remains a challenge for addressing neurological diseases. Researchers have modified adeno-associated virus (AAV9) capsids to transduce brain endothelial cells effectively in mice and rats. These modified AAVs also show superior transduction in non-human primates and ex vivo human brain slices, although the endothelial tropism is not conserved across species. The modified capsids can be used for serotype switching for sequential AAV administration in mice and genetically engineering the blood-brain barrier.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Craig Erker, Adam Lane, Brooklyn Chaney, Sarah Leary, Jane E. Minturn, Ute Bartels, Roger J. Packer, Kathleen Dorris, Nicholas G. Gottardo, Katherine E. Warren, Alberto Broniscer, Mark W. Kieran, Xiaoting Zhu, Peter White, Phillip J. Dexheimer, Katie Black, Anthony Asher, Mariko DeWire, Jordan R. Hansford, Sridharan Gururangan, Javad Nazarian, David S. Ziegler, Eric Sandler, Allison Bartlett, Stewart Goldman, Chie-Schin Shih, Tim Hassall, Hetal Dholaria, Pratiti Bandopadhayay, Yvan Samson, Michelle Monje, Paul G. Fisher, Andrew Dodgshun, Sarah Parkin, Murali Chintagumpala, Karen Tsui, David Gass, Valerie Larouche, Emmett Broxson, Mercedes Garcia Lombardi, Stacie Shiqi Wang, Jie Ma, Cynthia Hawkins, Dima Hamideh, Lars Wagner, Carl Koschmann, Christine Fuller, Rachid Drissi, Blaise Jones, James Leach, Maryam Fouladi
Summary: In patients with DIPG aged 10 years and older, long-term survivors are typically older with longer symptom duration, and have higher rates of ATRX mutations.
Article
Cardiac & Cardiovascular Systems
Jeffrey S. Bennett, David M. Gordon, Uddalak Majumdar, Patrick J. Lawrence, Adrianna Matos-Nieves, Katherine Myers, Anna N. Kamp, Julie C. Leonard, Kim L. McBride, Peter White, Vidu Garg
Summary: This study used a machine learning approach to predict pathogenic LMNA variants and identified a novel LMNA variant associated with conduction system disease. The results suggest that machine learning methods can assist in identifying high-risk variants of uncertain significance.
Article
Genetics & Heredity
Marilena Melas, Esko A. Kautto, Samuel J. Franklin, Mari Mori, Kim L. McBride, Theresa Mihalic Mosher, Ruthann B. Pfau, Maria Elena Hernandez-Gonzalez, Sean D. McGrath, Vincent J. Magrini, Peter White, Julie Balch Samora, Daniel C. Koboldt, Richard K. Wilson
Summary: Synpolydactyly 1, or syndactyly type II (SDTY2), is a genetic limb malformation characterized by polydactyly with syndactyly. The study identified heterozygous alterations in the HOXD13 gene associated with the disease, and highlighted the value of long-read whole-genome sequencing in elucidating the molecular etiology of congenital limb malformation disorders.
Article
Gastroenterology & Hepatology
Jacob M. Allen, Amy R. Mackos, Robert M. Jaggers, Patricia C. Brewster, Mikaela Webb, Chia-Hao Lin, Chris Ladaika, Ronald Davies, Peter White, Brett R. Loman, Michael T. Bailey
Summary: Psychological stress alters the gut microbiota and increases the risk for enteric infections and chronic bowel conditions. Stress disrupts colonic epithelial cells and mucosal integrity, leading to dysbiosis in the gut microbiota.
Article
Medicine, Research & Experimental
Swetha Ramadesikan, Scott Hickey, Emily De Los Reyes, Anup D. Patel, Samuel J. Franklin, Patrick Brennan, Erin Crist, Kristy Lee, Peter White, Kim L. McBride, Daniel C. Koboldt, Richard K. Wilson
Summary: Noncoding and synonymous coding variants that affect alternative splicing have been recognized as an important category of disease-causing variants. In this study, two siblings with hypotonia, developmental delays, and seizures were found to have compound-heterozygous variants in the SEPSECS gene. One variant disrupted protein translation while the other, predicted to be synonymous, affected mRNA splicing. Variations in the SEPSECS gene can cause a neurodegenerative disease.
COLD SPRING HARBOR MOLECULAR CASE STUDIES
(2022)
Meeting Abstract
Genetics & Heredity
Samantha Choi, Peter White, Bimal Chaudhari
GENETICS IN MEDICINE
(2022)
Article
Clinical Neurology
Summer R. Fair, Wesley Schwind, Dominic Julian, Alecia Biel, Gongbo Guo, Ryan Rutherford, Swetha Ramadesikan, Jesse Westfall, Katherine E. Miller, Meisam Naeimi Kararoudi, Scott E. Hickey, Theresa Mihalic Mosher, Kim L. McBride, Reid Neinast, James Fitch, Dean Lee, Peter White, Richard K. Wilson, Tracy A. Bedrosian, Daniel C. Koboldt, Mark E. Hester
Summary: Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions. In this study, a human cerebral organoid model was used to investigate the pathophysiology of a specific variant. The study found that the variant led to reduced growth and disrupted cell proliferation in the organoids. Gene editing was able to correct the variant and restore organoid growth and cell proliferative capacity. Single-cell RNA sequencing revealed changes in gene expression and signaling pathways. These findings highlight the importance of cerebral organoids in studying the molecular mechanisms underlying AUTS2 syndrome.
Article
Clinical Neurology
Tracy A. Bedrosian, Katherine E. Miller, Olivia E. Grischow, Kathleen M. Schieffer, Stephanie LaHaye, Hyojung Yoon, Anthony R. Miller, Jason Navarro, Jesse Westfall, Kristen Leraas, Samantha Choi, Rachel Williamson, James Fitch, Benjamin J. Kelly, Peter White, Kristy Lee, Sean McGrath, Catherine E. Cottrell, Vincent Magrini, Jeffrey Leonard, Jonathan Pindrik, Ammar Shaikhouni, Daniel R. Boue, Diana L. Thomas, Christopher R. Pierson, Richard K. Wilson, Adam P. Ostendorf, Elaine R. Mardis, Daniel C. Koboldt
Summary: This study identified somatic and germline variants associated with epilepsy in children, shedding light on the genetic basis of structural brain abnormalities leading to focal epilepsy and suggesting new candidate disease genes.
Article
Oncology
Flavia Watusi De Faria, Kathleen M. Schieffer, Christopher R. Pierson, Daniel R. Boue, Stephanie LaHaye, Katherine E. Miller, Nisreen Amayiri, Daniel C. Koboldt, Tara Lichtenberg, Kristen Leraas, Patrick Brennan, Ben Kelly, Peter White, Vincent Magrini, Richard K. Wilson, Elaine R. Mardis, Catherine E. Cottrell, Jerome Rusin, Jonathan L. Finlay, Diana S. Osorio
Summary: Ependymal tumors are the third most common brain tumor in children under 14 years old, and metastatic disease, although rare, has a negative prognosis especially in young children. Limited data is available on how to manage metastatic disease in patients under 3 years old. This study provides a literature review on clinical characteristics and radiation-sparing treatments for metastatic ependymoma in children under 3 years old. Chemotherapy-based approaches were used with radiation reserved for progression or relapse, and the overall survival rate varied among studies.
GENES CHROMOSOMES & CANCER
(2023)
Letter
Pediatrics
Joshua L. Bonkowsky, Tomi Pastinen, Peter White
PEDIATRIC RESEARCH
(2023)
Article
Genetics & Heredity
David M. Gordon, David Cunningham, Gloria Zender, Patrick J. Lawrence, Jacqueline S. Penaloza, Hui Lin, Sara M. Fitzgerald-Butt, Katherine Myers, Tiffany Duong, Donald J. Corsmeier, Jeffrey B. Gaither, Harkness C. Kuck, Saranga Wijeratne, Blythe Moreland, Benjamin J. Kelly, Vidu Garg, Peter White, Kim L. McBride
Summary: This study investigates the genetic causes of congenital heart disease by studying families with multiple individuals affected by heart defects. By identifying potential disease-causing genetic variants that are common among all affected individuals, the study was able to find plausible disease-causing variants in several genes and identify new genes that may contribute to the presence of a heart defect. The findings suggest that studying families may be more effective in finding causes of heart defects than studying individuals, and that changes in multiple genes may be required for a heart defect to occur.
Article
Oncology
Katherine E. Miller, Gregory Wheeler, Stephanie LaHaye, Kathleen M. Schieffer, Sydney Cearlock, Lakshmi Prakruthi Rao Venkata, Alejandro Otero Bravo, Olivia E. Grischow, Benjamin J. Kelly, Peter White, Christopher R. Pierson, Daniel R. Boue, Selene C. Koo, Darren Klawinski, Mark A. Ranalli, Ammar Shaikhouni, Ralph Salloum, Margaret Shatara, Jeffrey R. Leonard, Richard K. Wilson, Catherine E. Cottrell, Elaine R. Mardis, Daniel C. Koboldt
Summary: This study analyzed seven rhabdoid tumors from three pediatric patients using a multimodal molecular approach. The findings revealed SMARCB1 germline alterations in all patients and tumors, as well as different subgroups of rhabdoid tumors. The study also showed non-clonal origin of synchronous brain and kidney tumors, and suggested the likely origin of lung and abdominal metastasis. Other genetic events were identified in tumors but did not offer prognostic or therapeutic potential for rhabdoid tumors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pathology
Anthony R. Miller, Saranga Wijeratne, Sean D. McGrath, Kathleen M. Schieffer, Katherine E. Miller, Kristy Lee, Mariam Mathew, Stephanie LaHaye, James R. Fitch, Benjamin J. Kelly, Peter White, Elaine R. Mardis, Richard K. Wilson, Catherine E. Cottrell, Vincent Magrini
Summary: Molecular profiling using long-read sequencing improves the resolution of structural variations in cancer and enables the discovery of new expressed fusion partners and the analysis of complex intragenic alterations.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Review
Biotechnology & Applied Microbiology
Bram van de Sande, Joon Sang Lee, Euphemia Mutasa-Gottgens, Bart Naughton, Wendi Bacon, Jonathan Manning, Yong Wang, Jack Pollard, Melissa Mendez, Jon Hill, Namit Kumar, Xiaohong Cao, Xiao Chen, Mugdha Khaladkar, Ji Wen, Andrew Leach, Edgardo Ferran
Summary: There have been significant recent advances in single-cell technologies, especially in single-cell RNA sequencing (scRNA-seq), which are transforming drug discovery and development. These technologies are enhancing target identification, functional genomics screens, disease modeling, and drug response monitoring. Challenges and future directions in implementing these technologies in the pharmaceutical industry are also discussed.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Meeting Abstract
Pathology
M. Mathew, B. Bucknor, K. Schieffer, E. Varga, S. Choi, K. Miller, B. Kelly, P. White, R. Wilson, E. Mardis, C. Cottrell
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
