Alagille syndrome is a human autosomal dominant developmental disorder characterized by liver, heart, eye, skeletal, craniofacial and kidney abnormalities. caused mutations in the Jagged 1 (JAG1) gene, which encodes ligand for Notch family receptors. The majority of JAG1 seen patients are null alleles, suggesting haploinsufficiency as primary cause this disorder. Mice homozygous Jag1 mutation die during embryogenesis Jag1/+ heterozygous mice exhibit eye defects but do not other phenotypes...

Protein phosphatase 2A is a heterotrimeric protein serine/threonine consisting of 36-kDa catalytic C subunit, 65-kDa structural A and variable regulatory B subunit. The subunits determine the substrate specificity enzyme. There have been three families cellular identified to date: B55, B56 (B′), PR72/130. We now cloned five genes encoding human isoforms. Polypeptides encoded by all but one splice variant (B56γ1) are phosphoproteins, as shown mobility shift after treatment with alkaline...

The Notch gene family encodes large transmembrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. To assess the in vivo role Notch2 gene, we constructed a targeted mutation, Notch2(del1). Unexpectedly, found alternative splicing Notch2(del1) mutant allele leads to production two different in-frame transcripts delete either one or EGF repeats protein, suggesting this is hypomorphic mutation. Mice homozygous for mutation died perinatally from...

Protein phosphatase 2A (PP2A) is a major intracellular protein that regulates multiple aspects of cell growth and metabolism. The ability this widely distributed heterotrimeric enzyme to act on diverse array substrates largely controlled by the nature its regulatory B subunit. Only two gene families encoding endogenous subunits have been cloned date, although existence several additional likely. We identified two-hybrid interaction new human family PP2A subunits. This family, denoted B56,...

Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes ligand for Notch family receptors. A characteristic feature of intrahepatic bile duct paucity. We described previously that mice doubly heterozygous Jag1 and Notch2 are an excellent model syndrome. However, our previous study did not establish whether paucity Jag1/Notch2 double resulted from impaired differentiation precursor cells, or defects morphogenesis.Here we...

Abstract The Notch signaling pathway is an evolutionarily conserved intercellular mechanism, and mutations in its components disrupt embryonic development many organisms cause inherited diseases humans. We previously described construction analysis of a hypomorphic allele the Notch2 gene. Homozygosity for this leads to perinatal lethality due cardiovascular kidney defects. report here novel mutant alleles generated by gene targeting stem cells, including conditional null which exon 3 flanked...

Mutations in Notch receptors and their ligands have been identified as the cause of human congenital heart diseases, indicating importance signaling pathway during development. In our study, we use Cre-Lox technology to inactivate Notch2 several cardiac cell lineages determine functional requirements for mammalian Inactivation neural crest cells resulted abnormally narrow aortas pulmonary arteries due a decrease smooth muscle tissue. The reduction tissue was not migration defects but instead...

The Caenorhabditis elegans maternal-effect clk genes are involved in the temporal control of development and behavior. We report genetic molecular characterization clk-2. A temperature-sensitive mutation gene clk-2 affects embryonic post-embryonic development, reproduction, rhythmic behaviors. Yet, virtually all phenotypes fully maternally rescued. Embryonic strictly requires activity maternal during a narrow time window between oocyte maturation two- to four-cell stage. Positional cloning...

Protein Phosphatase 2A (PP2A) function is controlled by regulatory subunits that modulate the activity of catalytic subunit and direct PP2A complex to specific intracellular locations. To study PP2A's role in signal transduction pathways control growth differentiation vivo, a transgenic mouse lacking B56γ was made.Lack PP2A-B56γ holoenzyme, resulted formation an incomplete ventricular septum decrease number cardiomyocytes. During cardiac development, expressed nucleus α-actinin-positive...

A disintegrin and metalloproteinase 10 (ADAM10) is a zinc-dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as key regulator of cellular processes by cleaving shedding extracellular domains multiple transmembrane receptors ligands. We have developed B cell-specific ADAM10-deficient mice (ADAM10(B-/-)). In this study, we show that levels are significantly enhanced on germinal center cells. Moreover, ADAM10(B-/-) had severely diminished primary secondary responses...

<i>clk-1</i> has been identified and characterized in the nematode <i>Caenorhabditis elegans</i> as a gene that affects rates, regularity, synchrony of physiological processes. The CLK-1 protein is mitochondrial required for ubiquinone biosynthesis yeast worms, but its biochemical function remains unclear. We have studied expression murine<i>mclk1</i> variety tissues, we find pattern <i>mclk1</i> mRNA accumulation closely resembles genes involved oxidative phosphorylation. accumulation,...

The Notch receptor is a key component of highly conserved signaling pathway that regulates cell fate determination during development. In Drosophila, where was first identified and studied, there only one receptor. contrast, mammals have four genes, Notch1-4. Notch1 Notch2 are both required for embryo viability, widely expressed in mammals, structurally conserved. It presently unknown if these two receptors functionally redundant or they unique capabilities related to differences their amino...

The Spindle Assembly Checkpoint (SAC) is part of a complex feedback system designed to ensure that cells do not proceed through mitosis unless all chromosomal kinetochores have attached spindle microtubules. formation the kinetochore and implementation SAC are regulated by multiple kinases phosphatases. BubR1 phosphoprotein Cdc20 containing mitotic checkpoint inhibits APC/C so Cyclin B1 Securin degraded, thus preventing going into anaphase. In this study, we found PP2A in association with...

Protein phosphatase 2A (PP2A) is a heterotrimeric that controls wide range of cellular functions. The catalytic activity and intracellular location PP2A are modulated by its association with regulatory B subunits, including B56 proteins, which encoded five separate genes in humans mice. specific effects each protein on function largely unknown. As part an effort to identify PP2A-B56 functions, we created knockout strains B56β, B56δ, B56ε using CRISPR/Cas9n. We found none the individual...

To enhance RF safety when implantable medical devices are located within the body coil but outside imaging region by using a secondary resonator (SR) to reduce electric fields, corresponding specific absorption rate (SAR), and temperature change during MRI.This study was conducted numerical simulations with an American Society for Testing Materials (ASTM) phantom adult human models of Ella Duke from Virtual Family Models, along experimental results obtained ASTM phantom. The circular SR...

This study describes the MRI-related radio frequency (RF) safety evaluation of breast tissue expander devices to establish criteria. Numerical simulations and experimental measurements were performed at 64 MHz with a gel phantom containing expander. Additionally, computational modeling was (64 128 MHz) an adult female model, virtually implanted device for four imaging landmark positions. The presence led significant alterations in specific absorption rate (SAR) and|B1+|distributions. main...

This study investigates the use of pads with high dielectric constant (HDC) materials to alter electromagnetic field distributions in patients during magnetic resonance imaging (MRI). The was performed numerical simulations and phantom measurements. An initial proof-of-concept validation using a at 64 MHz, showing increases up 10% when distilled water as material. Additionally, computational models human anatomy were 128 MHz. Results these barium titanate (BaTiO3) beads showed 61% increase...