Abstract Background MicroRNAs are a large new class of tiny regulatory RNAs found in nematodes, plants, insects and mammals. thought to act as post-transcriptional modulators gene expression. In invertebrates microRNAs have been implicated regulators developmental timing, neuronal differentiation, cell proliferation, programmed death fat metabolism. Little is known about the roles Results We isolated 18-26 nucleotide from developing rat monkey brains. From sequences these human genomes we...

A good correlation was observed between enhanced lung cancer risk and restriction fragment length polymorphisms (RFLPs) of the P450IA1 gene with enzyme Msp I. Genotype frequencies 0.49 for predominant homozygote, 0.40 heterozygote, 0.11 homozygous rare allele were in a healthy population. Among patients, frequency found to be about 3‐fold higher than that among population, this difference statistically significant. This is first report identify genetically high individuals at level.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate synaptic plasticity. triggers three downstream signaling pathways; Phosphatidylinositol 3-kinase (PI3K), Phospholipase Cγ (PLCγ) Mitogen activated protein kinases/Extracellular signal-regulated kinases (MAPK/ERK). We previously showed two distinct mechanisms whereby BDNF-TrkB pathway controls trafficking of PSD-95, which is the major scaffold at excitatory synapses critical for synapse maturation. BDNF activates PI3K-Akt...

The N -methyl- d -aspartate (NMDA) glutamate receptor (NMDAR), long implicated in developmental plasticity, shows decay time kinetics that shorten postnatally as NR2A subunits are added to the receptor. Neither mechanism nor immediate effect of this change is known. We studied developing NMDAR currents by using visual neurons slices from knockout (NR2AKO) and WT mice. Both strains show increased dendritic levels synaptic density scaffolding protein PSD-95 with age. Dendritic at same...

The membrane-associated guanylate kinase PSD-95 scaffolds N -methyl- d -aspartate receptors to cytoplasmic signaling molecules, and associates with other glutamate at central synapses. However, regulation of in vivo is poorly understood. We provide evidence an activity-dependent redistribution dendrites visual neurons that tied eye opening. Six hours after opening, increased dendritic coimmunoprecipitates the same proportions stargazin, receptor subunit NR2A, decreased NR2B. Sustained high...

Postsynaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, onset of pattern vision, triggers a rapid movement PSD-95 from visual neuron somata to synapses. We showed previously that PI3 kinase–Akt pathway downstream BDNF/TrkB signaling stimulates synaptic delivery via vesicular transport. However, transport requires palmitoylation attach it lipid membrane. Also, insertion synapses known require this...

Protein palmitoylation and depalmitoylation alter protein function. This post-translational modification is critical for synaptic transmission plasticity. Mutation of the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) causes infantile neuronal ceroid lipofuscinosis (CLN1), a pediatric neurodegenerative disease. However, role in maturation unknown. Therefore, we studied synapse development Ppt1-/- mouse visual cortex. We demonstrate that developmental N-methyl-D-aspartate...

To understand the role of estrogen in pathogenesis benign prostatic hyperplasia, expressions receptor (ER) mRNA and ER protein by situ hybridization immunohistochemistry, respectively, were investigated human tissues. In non-malignant region, found cytoplasm nucleus, stromal cells, but not glandular epithelial basal cells. regions, mRNA/ER positive cells fibromyoadenomatous myoadenomatous adenomatous hyperplasia. A striking feature was periacinar arrangement all prostate carcinoma treated...

Assessments of RNA integrity and its hybridizability are essential for successful implementation in situ hybridization (ISH) mRNA or viral RNA, particularly when paraffin-embedded specimens from surgical, biopsy, autopsy cases used. In this study, we examined the suitability ISH 28S ribosomal (rRNA) purpose. Oligo-DNA with nucleotide sequences complementary to a well-conserved segment rRNA auxiliary adenine-thymine-thymine (ATT) repeats at 3' 5' ends was synthesized. The oligo-DNA made...

Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which shift balance between excitation inhibition. To decipher the substrate of hyperexcitability, we examined pan-neuronal Tsc1 knockout mouse found reduction in surface expression GABA receptor (GABAR) subunit but not AMPA (AMPAR) subunit. Using electrophysiological recordings, significant...

Myosin Va (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but role of MyoVa in synaptic development function largely unknown. Here, studies using dominant-negative neurological mutant mouse Flailer, we find that plays an essential activity-dependent delivery PSD-95 other critical PSD molecules to synapses endocytosis AMPA-type glutamate receptors (AMPAR) dendrites CNS neurons. known carry a complex...

Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder affecting the brain and other vital organs. Neurological symptoms include epilepsy, intellectual disability, autism. TSC caused by a loss-of-function mutation in TSC1 or TSC2 gene. These gene products form protein normally suppress mammalian target of rapamycin (mTOR) activity. mTOR inhibitors have been used to treat subependymal glioma (SEGA) that tumor characteristic TSC. However, neuropathology also involves...

Palmitoylation and depalmitoylation represent dichotomic processes by which a labile posttranslational lipid modification regulates protein trafficking degradation. The depalmitoylating enzyme, palmitoyl-protein thioesterase 1 (PPT1), is associated with the devastating pediatric neurodegenerative condition, infantile neuronal ceroid lipofuscinosis (CLN1). CLN1 characterized accumulation of autofluorescent lysosomal storage material (AFSM) in neurons robust neuroinflammation. Converging lines...

Infantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in the CLN1 gene, which encodes depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results death, typically before fifteen years of age. Histopathological features include aggregation autofluorescent material (AFSM), as...

Protein palmitoylation is the only reversible post-translational lipid modification. Palmitoylation held in delicate balance by depalmitoylation to precisely regulate protein turnover. While over 20 enzymes are known, conducted fewer enzymes. Of particular interest lack of depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) that causes devastating pediatric neurodegenerative condition infantile neuronal ceroid lipofuscinosis (CLN1). most research on Ppt1 function has centered its...

In Prader–Willi syndrome, the neuropathologic abnormalities causative for central hypotonia or cognitive delay are largely unknown. We report a girl diagnosed with syndrome in whom cranial MRI showed diffusely abnormal cerebral gyral folding pattern strongly suggestive of cortical malformation. The patient was born to 27-year-old mother. The pregnancy normal prior cesarean section performed at 35 weeks gestational age because vaginal bleeding from placenta previa. Apgar scores were 4 1...