Hydrocephalus is a serious condition that impacts patients of all ages. The standards care are surgical options to divert, or inhibit production of, cerebrospinal fluid; date, there no effective pharmaceutical treatments, our knowledge. causes vary widely, but one commonality this aberrations in salt and fluid balance. We have used genetic model hydrocephalus show ventriculomegaly can be alleviated by inhibition the transient receptor potential vanilloid 4, channel activated changes osmotic...

Cells are often cultured at high density (e.g., confluent monolayer and as pellets) to promote chondrogenic differentiation maintain the chondrocyte phenotype. They also frequently suspended in hydrogels such agarose or alginate for same purposes. These culture techniques differ markedly with respect frequency of direct contact between cells overall intercellular spacing. Because these factors may significantly affect mechanotransduction, purpose this study was determine if response...

Moderate loads with knee loading enhance bone formation, but its effects on the maintenance of are not well understood. In this study, we examined activity matrix metalloproteinase13 (MMP13) and evaluated role p38 MAPK Rac1 GTPase in regulation MMP13.Knee (0.5-3 N for 5 min) was applied to right surgically-induced osteoarthritis (OA) mice as normal (non-OA) mice, MMP13 femoral cartilage examined. The sham-loaded used a non-loading control. We also employed primary non-OA OA human...

Recent studies have implicated a role of norepinephrine (NE) in the activation sodium chloride cotransporter (NCC) to drive development salt-sensitive hypertension. However, interaction between NE and increased salt intake on blood pressure remains be fully elucidated. This study examined impact continuous infusion homeostasis conscious Sprague-Dawley rats challenged with normal (NS; 0.6% NaCl) or high-salt (HS; 8% diet for 14 days. Naïve saline-infused remained normotensive when placed HS...

Abstract Transmembrane protein 67 (TMEM67) is mutated in Meckel Gruber Syndrome type 3 (MKS3) resulting a pleiotropic phenotype with hydrocephalus and renal cystic disease both humans rodent models. The precise pathogenic mechanisms remain undetermined. Herein it reported for the first time that point mutation of TMEM67 leads to gene dose-dependent hydrocephalic Wistar polycystic kidney (Wpk) rat. Animals heterozygous mutations manifest slowly progressing hydrocephalus, observed during...

Heparin binding epidermal growth factor-like factor (HB-EGF) is an angiogenic mediating radial migration of the developing forebrain, while vascular endothelial (VEGF) known to influence rostral migratory stream in rodents. Cell defects have been identified animal models hydrocephalus; however, relationship between HB-EGF and hydrocephalus unclear. We show that mice overexpressing human with β-galactosidase reporter exhibit elevated VEGF, localization outside subventricular zone (SVZ),...

The intervertebral disc is composed of load-bearing fibrocartilage that may be subjected to compressive forces up 10 times the body weight. multilaminated outer layer, annulus fibrosus (AF), vulnerable damage and its regenerative potential limited, sometimes leading nuclear herniation. Scaffold-based tissue engineering AF using stem cell technology has enabled development bi-laminate constructs after weeks culture. It difficult know if these are limited by differentiation state cells or...

Mutations of ion channels and G-protein-coupled receptors (GPCRs) are not uncommon can lead to cardiovascular diseases. Given previously reported multiple factors associated with high mutation rates, we sorted the relative mutability human genes by (i) proximity telomeres and/or (ii) adenine thymine (A+T) content. We extracted genomic information using genome data viewer examined 118 channel 143 GPCR based on their association (ii). then assessed these two 31 encoding or GPCRs that targeted...

Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer’s disease (AD) are somewhat similar, it is common to misdiagnose these two conditions. Although there fluid markers detectable in humans with NPH AD, determining which biomarker optimal representing genetic characteristics consistent throughout species poorly understood. Here, we hypothesize that can be differentiated from AD mRNA biomarkers unvaried proximity telomeres. We examined human caudate nucleus tissue samples for the...

Undifferentiated connective tissue that arises during embryonic development and some healing processes contains pluripotent mesenchymal stem cells. It is becoming increasingly evident the mechanical environment an important differentiation factor for these In our laboratory, we have focused on potential signals to induce chondrogenic of Using C3H10T1/2 cells as a model, investigated influence hydrostatic pressure, equibiaxial contraction, centrifugal pressure chondroinduction. Cells...

Monogenic hypertension is rare and caused by genetic mutations, but whether factors associated with mutations are disease-specific remains uncertain. Given two high mutation rates, we tested how many previously known genes match (i) proximity to telomeres or (ii) adenine thymine content in cardiovascular diseases (CVDs) related vascular stiffening. We extracted genomic information using a genome data viewer. In human chromosomes, 64 of 79 loci involving >25 single nucleotide polymorphisms...

Sustaining brain serotonin is essential in mental health. Physical activities can attenuate problems by enhancing signaling. However, such activity not always possible disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects voluntary exercise. Focusing on serotonergic signaling, we addressed question: Does local mechanical loading the skeleton elevate expression tryptophan hydroxylase 2 (tph2) that rate-limiting enzyme for...

Cyclic hydrostatic pressure of physiological magnitude (< 10 MPa) stimulates chondrogenic differentiation mesenchymal stem cells, but mechanotransduction mechanisms are not well understood. It was hypothesized that an intact cytoskeleton would be required for uninhibited pressure. Therefore we examined the effects drugs which selectively interfere with actin and tubulin polymerization on pressure-induced upregulation aggrecan col2a1 (type II collagen) mRNA expression. C3H10T1/2 cells were...

Background Vascular endothelial growth factor A (VEGF-A) is a member of the larger family VEGF-related cytokines that mediates multiple functions cells including proliferation, migration, and permeability. Current thinking on pathogenesis communicating hydrocephalus focuses pulsatile vascular mechanisms, but biochemical biological underpinnings remain obscure. Insertion shunt, most common treatment this disorder, often fails. We wished to begin exploration link between hyperpulsatility...

Abstract Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) are similar, it is not uncommon to misdiagnose these two conditions. Although increasing evidence supports that neuroinflammation detectable in humans with NPH AD alike, which resident or infiltrating cell expressing mRNA markers mediates remains poorly understood. Here, we hypothesize can be differentiated from biomarkers unvaried proximity telomeres CD8+ T cells affect neurodegeneration. We examined human...

The glucagon-like peptide-1 receptor (GLP-1R) agonists reduce glycated hemoglobin in patients with type 2 diabetes. Mounting evidence indicates that the potential of GLP-1R agonists, mimicking a 30 amino acid ligand, GLP-1, extends to treatment neurodegenerative conditions, particular focus on Alzheimer's disease (AD). However, mechanism underlies regulation availability brain AD remains poorly understood. Here, using whole transcriptome RNA-Seq human postmortem caudate nucleus and chronic...

Mutations of protein kinases and cytokines are common can cause cancer other diseases. However, our understanding the mutability in these genes remains rudimentary. Therefore, given previously known factors which associated with high mutation rates, we analyzed how many encoding druggable match (i) proximity to telomeres or (ii) A+T content. We extracted this genomic information using National Institute Health Genome Data Viewer. First, among 129 human kinase studied, 106 satisfied either...