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Safely and efficiently controlling gene expression is a long-standing goal of biomedical research, and the recently discovered bacterial CRISPR/Cas system can be harnessed to create powerful tools for epigenetic editing. Current state-of-the-art systems consist of a deactivated-Cas9 nuclease (dCas9) fused to one of several epigenetic effector motifs/domains, along with a guide RNA (gRNA) which defines the genomic target. Such systems have been used to safely and effectively silence or activate a specific gene target under a variety of circumstances.
View Article and Find Full Text PDFApoE: A new piece to the severe malaria puzzle.
Pediatr Res
July 2024
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Menopausal Hormone Therapy and the Mind: The Role of Hormone Replacement in the Prevention and Treatment of Cognitive Decline, Dementia, and Cognitive Dysfunction of Depression.
Harv Rev Psychiatry
July 2022
From Harvard Medical School; Department of Psychiatry (Drs. Koire and Joffe), Connors Center for Women's Health and Gender Biology (Dr. Joffe), and Center for Alzheimer Research and Treatment, Department of Neurology (Dr. Buckley), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston, MA (Dr. Buckley); Melbourne School of Psychological Science and Florey Institutes, University of Melbourne (Dr. Buckley).
Learning Objectives: After participating in this activity, learners should be better able to:• Outline the clinical recommendations for menopausal hormone treatment related to cognitive concerns• Debate and discuss the various research pieces on the use of menopausal hormone therapy cognitive decline, dysfunction, and dementia.
Abstract: Menopause has been associated with subjective cognitive dysfunction and elevated rates of depression. While menopausal hormone therapy (MHT) is Food and Drug Administration-approved for the treatment of vasomotor symptoms related to menopause, a potential role for MHT in treating and preventing cognitive decline, dysfunction, and dementia has remained unclear and a topic of continued interest and debate across decades of research.
PERHAPS: Paired-End short Reads-based HAPlotyping from next-generation Sequencing data.
Brief Bioinform
July 2021
School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.
The identification of rare haplotypes may greatly expand our knowledge in the genetic architecture of both complex and monogenic traits. To this aim, we developed PERHAPS (Paired-End short Reads-based HAPlotyping from next-generation Sequencing data), a new and simple approach to directly call haplotypes from short-read, paired-end Next Generation Sequencing (NGS) data. To benchmark this method, we considered the APOE classic polymorphism (*1/*2/*3/*4), since it represents one of the best examples of functional polymorphism arising from the haplotype combination of two Single Nucleotide Polymorphisms (SNPs).
View Article and Find Full Text PDFBeta-amyloid pathology in human brain microvessel extracts from the parietal cortex: relation with cerebral amyloid angiopathy and Alzheimer's disease.
Acta Neuropathol
May 2019
Faculté de pharmacie, Université Laval, Quebec, QC, Canada.
Several pieces of evidence suggest that blood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD), exemplified by the frequent occurrence of cerebral amyloid angiopathy (CAA) and the defective clearance of Aβ peptides. However, the specific role of brain microvascular cells in these anomalies remains elusive. In this study, we validated by Western, ELISA and immunofluorescence analyses a procedure to generate microvasculature-enriched fractions from frozen samples of human cerebral cortex.
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