Basic Science and Pathogenesis.

Background: Herpes simplex virus (HSV-1) has been associated with molecular and cellular signatures associated with Alzheimer's disease (AD). We explored the use of both recent single-cell and bulk transcriptomics technologies in dissecting the molecular and cellular virus-human interactions with HSV-1 infected cerebral organoids (2D and 3D). We compared the results with our previous observations from bulk RNA sequencing and discovered novel insights into HSV-1 induced AD-associated molecular pathology that were made possible by each transcriptomics technology.

Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain.

Introduction: While there may be microbial contributions to Alzheimer's disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).

Methods: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Organoid-Specific Transcripts Associated with Alzheimer's Disease and Autoimmune Diseases.

Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer's disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D.

Choroid plexus extracellular vesicle transport of blood-borne insulin-like growth factor 1 to the hippocampus of the immature brain.

Reduced serum level of insulin-like growth factor 1 (IGF-1), a major regulator of perinatal development, in extremely preterm infants has been shown to be associated with neurodevelopmental impairment. To clarify the mechanism of IGF-1 transport at the blood-cerebrospinal fluid (CSF) barrier of the immature brain, we combined studies of in vivo preterm piglet and rabbit models with an in vitro transwell cell culture model of neonatal primary murine choroid plexus epithelial (ChPE) cells. We identified IGF-1-positive intracellular vesicles in ChPE cells and provided data indicating a directional transport of IGF-1 from the basolateral to the apical media in extracellular vesicles (EVs).

Characteristics of preschool-age children who engage in problematic sexual behaviors with siblings.

Background: Problematic sexual behavior (PSB) between siblings can be a form of sibling sexual abuse (SSA). A notable gap in research are studies examining PSB among preschool-age children with siblings.

Objective: This study examined the impact of child maltreatment, exposure to family sexuality, and use of coercive sexual behavior on preschool-aged children PSB with siblings and with nonsiblings.