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Archive - Apr 29, 2017

Zika Virus Persists in Central Nervous System and Lymph Nodes of Rhesus Monkeys

Zika virus can persist in cerebrospinal fluid (CSF), lymph nodes, and colorectal tissue of infected rhesus monkeys for weeks after the virus has been cleared from blood, urine, and mucosal secretions, according to a study published online on April 27, 2017 in Cell. The article is titled “Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys.” The research was led by Dan H. Barouch, MD, PhD, and colleagues at Beth Israel Deaconess Medical Center and Harvard Medical School and was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. Investigators infected 20 rhesus monkeys with Zika virus and noted that, although virus was cleared from peripheral blood within 7-10 days, it was detected in CSF for up to 42 days and in lymph nodes and colorectal tissue for up to 72 days. Immunologic data showed that the emergence of Zika virus-specific neutralizing antibodies correlated with the rapid control of the virus in plasma. However, Zika-specific antibodies were not detected in CSF, which could be why the virus remained there longer. The authors also found that viral persistence in CSF correlated with the activation of the mechanistic target of rapamycin (mTOR) pathway, which has been shown to be related to the development of brain tissue and brain malformations. The findings suggest that persistent virus in the central nervous system may contribute to the neurological issues associated with Zika virus infection in people, the authors note. Although Zika virus usually causes mild or no symptoms in people, it has been associated with neurological disorders in children and adults and can cause severe fetal defects, such as microcephaly, if an infected pregnant woman passes the virus to her fetus.

CRISPR Used to Edit Stem Cells to Fight Arthritis in Joints

Using new gene-editing technology, researchers have rewired mouse stem cells to fight inflammation caused by arthritis and other chronic conditions. Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy), develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation. The cells were developed at Washington University School of Medicine in St. Louis and Shriners Hospitals for Children-St. Louis, in collaboration with investigators at Duke University and Cytex Therapeutics Inc., both in Durham, N.C. The researchers initially worked with skin cells taken from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation. The research was published online on April 27, 2017 in the journal Stem Cell Reports. The open-access article is titled “Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs.” "Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed," said Farshid Guilak, PhD, the paper's senior author and a Professor of Orthopedic Surgery at Washington University School of Medicine. "To do this, we needed to create a 'smart' cell."

New Study Yields Data Suggesting Revision of Prevailing Thoughts on Development and Evolutionary Origin of Vertebrate Brain

A study published online on April 19, 2017 in PLOS Biology provides information that substantially changes the prevailing idea about the brain formation process in vertebrates and sheds some light on how it might have evolved. The open-access article is titled “Molecular Regionalization of the Developing Amphioxus Neural Tube Challenges Major Partitions of the Vertebrate Brain.” The findings show that the interpretation maintained hitherto regarding the principal regions formed at the beginning of vertebrate brain development is not correct. This research was led jointly by the researchers José Luis Ferran and Luis Puelles of the Department of Human Anatomy and Psychobiology organism, albeit very close to us in evolutionary terms, therefore it gives us some insights as to what our ancestors might have been like. Hence, by comparing the territories of the modern vertebrate brain to that of amphioxus, we analyzed what might have occurred to lead them to multiply and how such a complex structure was formed in the course of our evolution,” explained the lecturer of the Department of Human Anatomy and Psychobiology of the University of Murcia (UMU) José Luis Ferrán, PhD, one of the researchers. "In this study, we used genoarchitecture as our main experimental framework to determine the regionalization of the amphioxus neural tube and compare it to that of vertebrates. Within this framework, we generated a molecular map of gene expression patterns in amphioxus, whose homologs are known to be involved in establishment and regionalization of the vertebrate brains" explains Beatriz Albuixech-Crespo (Dept Genética, Microbiología y Estadística UBof the UMU; Manuel Irimia of the Centre for Genomic Regulation (CRG), and Jordi García Fernández of the Genetics Department of the University of Barcelona.