The blood-brain barrier (BBB) formed by brain endothelial cells interconnected tight junctions is essential for the homeostasis of central nervous system. Although studies have shown importance various signaling molecules in BBB formation during development, little known about molecular basis regulating integrity adult BBB.Using a mouse model with tamoxifen-inducible cell-restricted disruption ctnnb1 (iCKO), we show here that β-catenin maintaining and system mice. iCKO mice developed severe...

It is becoming increasingly clear that herpesviruses can exploit the endocytic pathway to infect cells, yet several important features of this process remain poorly defined. Using herpes simplex virus-1 (HSV-1) as a model, we demonstrate endocytosis virions mimic many phagocytosis. During entry, HSV-1 associated with plasma membrane protrusions followed by phagocytosis-like uptake involving rearrangement actin cytoskeleton and trafficking in large phagosome-like vesicles. RhoA GTPase was...

Autophagy is a process by which cells recycle cytoplasm and defective organelles during stress situations such as nutrient starvation. It can also be used host an immune defense mechanism to eliminate infectious pathogens. Here we describe the use of autophagy survival virulence-associated trait human fungal pathogen Cryptococcus neoformans. We report that mutant form C. neoformans lacking Vps34 PI3K (vps34Delta), known involved in ascomycete yeast, was formation autophagy-related 8-labeled...

Abstract Virtually all efforts to generate an effective protection against the life-long, recurrent genital infections caused by HSV-2 have failed. Apart from sexual transmission, virus can also be transmitted mothers neonates, and it is a key facilitator of HIV coacquisition. In this article, we uncover nanoimmunotherapy using specially designed zinc oxide tetrapod nanoparticles (ZOTEN) with engineered oxygen vacancies. We demonstrate that ZOTEN, when used intravaginally as microbicide,...

Abstract As a means to understand human neuropsychiatric disorders from brain samples, we compared the transcription patterns and histological features of postmortem fresh neocortex isolated immediately following surgical removal. Compared number disease-associated transcriptomes, transcriptome had an entirely unique transcriptional pattern. To this difference, measured genome-wide as function time after tissue removal mimic interval. Within few hours, selective reduction in neuronal...

The study of regulatory networks in human pathogens such as Cryptococcus neoformans provides insights into host-pathogen interactions that may allow for correlation gene expression patterns with clinical outcomes. In the present study, deletion cryptococcal copper-dependent transcription factor 1 (Cuf1) led to defects growth and virulence low copper conditions. mouse models, cuf1Delta strains exhibited reduced dissemination brain, but no change lung growth, suggesting is limiting neurologic...

The exact incidence of pineal germ-cell tumors is largely unknown. are rare, and the number patients with these tumors, as reported in clinical series, has been limited. goal this study was to describe a large patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, End Results (SEER) database (1973-2001); Central Brain Tumor Registry United States (CBTRUS; 1997-2001); National Cancer Data Base (NCDB; 1985-2003). Tumors...

Abstract Increase in prostaglandin (PG) E 2 levels and oxidative damage are associated with diseases of brain that involve activation innate immunity. We tested the hypothesis cerebral resulting from immunity intracerebroventricular (icv) lipopolysaccharide (LPS) is dependent on PGE ‐mediated signaling. measured two quantitative vivo biomarkers lipid peroxidation: F ‐isoprostanes (IsoPs) derive arachidonic acid (AA) uniformly distributed all cell types brain, 4 ‐neuroprostanes (NeuroPs)...

Herpes simplex virus type 1 (HSV-1) infection of the corneal stroma remains a major cause blindness. Primary cultures fibroblasts (CF) were tested and found susceptible to HSV-1 entry, which was confirmed by deconvolution imaging infected cells. Plaque assay real-time PCR demonstrated viral replication hence productive CF HSV-1. A role for glycoprotein D (gD) receptors in cultured determined gD interference assay. Reverse transcription-PCR analysis indicated expression herpesvirus entry...

Heparan sulfate (HS) and its highly modified form, 3-O-sulfated heparan (3-OS HS), contribute strongly to herpes simplex virus type-1 (HSV-1) infection in vitro. Here we report results from a random M13-phage display library screening isolate 12-mer peptides that bind specifically HS, 3-OS block HSV-1 entry. The identified representative candidates two-different groups of anti-HS with high positive charge densities. Group 1, represented by G1 peptide (LRSRTKIIRIRH), belongs class alternating...

Abstract Fast-replicating neurotropic herpesviruses exemplified by herpes simplex virus-1 (HSV-1) naturally infect the central nervous system (CNS). However, most individuals intrinsically suppress virus during a primary infection and preclude it from significantly damaging CNS. Optineurin (OPTN) is conserved autophagy receptor with little understanding of its role in viral infections. We show that OPTN selectively targets HSV-1 tegument protein, VP16, fusion glycoprotein, gB, to degradation...

Mammalian reoviruses are non-enveloped viruses that contain a segmented, double-stranded RNA genome. Reoviruses infect most mammalian species, although infection with these in humans is usually asymptomatic. We report the isolation of novel reovirus strain from 6.5-week-old child meningitis. Hemagglutination and neutralization assays indicated isolate serotype 3 strain, leading to designation T3/Human/Colorado/1996 (T3C/96). Sequence analysis T3C/96 S1 gene segment, which encodes viral...

The study of fungal regulatory networks is essential to the understanding how these pathogens respond host environmental signals with effective virulence-associated traits. In this study, a DEAD-box RNA helicase–encoding gene (VAD1) was isolated from mutant defective in virulence factor laccase. A Δvad1 exhibited profound reduction mouse model that restored after reconstitution WT VAD1. Loss VAD1 resulted upregulation NOT1, encoding global repressor transcription. NOT1 found act as an...

purpose. The human conjunctiva is a natural target for herpes simplex virus (HSV)-1 infection. goals of this study were to investigate the cellular and molecular mechanisms HSV-1 entry into conjunctival epithelial (HCjE) cells. Specific features studied included method initial viral binding cells, pH dependency, expression usage specific receptors. methods. To observe binding, live cell imaging was performed on HSV-1–infected HCjE Reporter virions expressing β-galactosidase used determine...

Herpes simplex virus type 1 (HSV-1) is an important human pathogen and a leading cause of infectious blindness in the developed world. HSV-1 exploits heparan sulfate proteoglycans (HSPG) for attachment to cells. While significance sulphate (HS) moieties infection well established, role specific proteoglycan core proteins process remains poorly understood. The objective this study was assess roles syndecan-1 syndecan-2 infection, both which are expressed by many target cell types. Our results...

ABSTRACT The γ 1 34.5 protein of herpes simplex viruses (HSV) is essential for viral pathogenesis, where it precludes translational arrest mediated by double-stranded-RNA-dependent kinase (PKR). Paradoxically, inhibition PKR alone not sufficient HSV to exhibit virulence. Here we report that inhibits TANK binding (TBK1) through its amino-terminal sequences, which facilitates replication and neuroinvasion. Compared wild-type virus, the mutant lacking amino terminus induces stronger antiviral...

Although epilepsy is associated with a variety of abnormalities, exactly why some brain regions produce seizures and others do not known. We developed method to identify cellular changes in human epileptic neocortex using transcriptional clustering. A paired analysis high low spiking tissues recorded vivo from 15 patients predicted 11 cell-specific together their 'cellular interactome'. These predictions were validated histologically revealing millimetre-sized 'microlesions' global increase...

Infection of neonatal mice with some reovirus strains produces a disease similar to infantile biliary atresia, but previous attempts correlate infection this have yielded conflicting results. We used isogenic T3SA– and T3SA+, which differ solely in the capacity bind sialic acid as coreceptor, define role encephalitis tract mice. Growth intestine was equivalent for both following peroral inoculation. However, T3SA+ spread more rapidly from distant sites replicated higher titers spleen, liver,...

In a mouse model for herpes simplex virus type 1 (HSV-1) latency in which the was inoculated via eye after corneal scarification, HSV-1 replicated epithelial cells and infected nerve cell endings. reached trigeminal ganglia by fast axonal transport between 2 10 days postinfection (p.i.) established latent infection neuronal or spread to nonneuronal cells. By using situ hybridization, we showed that cellular transcription factors are stimulated ganglia. This stimulation is biphasic, peaking...

Reovirus induces apoptosis in cultured cells and vivo. In cell culture models, is contingent upon a mechanism involving reovirus-induced activation of transcription factor NF-κB complexes containing p50 p65/RelA subunits. To explore the vivo role this process, we tested capacity reovirus to induce mice lacking functional nfkb1/p50 gene. The genetic defect had no apparent effect on replication intestine or dissemination secondary sites infection. comparison what was observed wild-type...