Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) promote the function and/or survival of basal forebrain (BF) cholinergic neurons in vivo and in culture. The neurotrophin source is commonly thought to be targets of cholinergic neurons and the possibility that local glial sources support cholinergic neurons has not been well examined. These sources, however, may be critical to BF neurons before or even after they reach their targets.

Cloning and identification of a novel human RNPC3 gene that encodes a protein with two RRM domains and is expressed in the cell nucleus.

The RNA recognition motifs (RRM) domain is one of the most common eukaryotic protein folds. Proteins containing RRM domains function in important steps of posttranscriptional regulation of gene expression and are involved in processing and transport of mRNA precursors. Here we describe the cloning and characterization of a novel human RNPC3 gene containing two RNA recognition motifs.

Transcriptional analysis of mouse skeletal myofiber diversity and adaptation to endurance exercise.

Vertebrate skeletal myofibers are heterogeneous with respect to their metabolic, contractile and morphological properties. To better understand skeletal myofiber diversity and plasticity at the transcriptional level, we carried out a whole-genome gene expression analysis of skeletal muscles composed primarily of slow/oxidative fibers (soleus) and fast fibers (extensor digitorum longus, EDL). We also followed gene expression changes in plantaris muscles from mice undergoing voluntary wheel running, a protocol that triggers transformation of glycolytic fibers into oxidative ones.

Identification of a novel liver-specific expressed gene, TCP10L, encoding a human leucine zipper protein with transcription inhibition activity.

The incidence of hepatoma is high in the Chinese population. Searching for genes involved in the functions of the liver, especially genes specifically expressed in the liver, will facilitate an insight into the molecular basis of normal and abnormal liver functions. Based on a differentially displayed cDNA fragment, which was down regulated in hepatoma tissues, we cloned a novel cDNA of 957 bp, TCP10L (T-complex protein 10 like), from the human liver cDNA library.

Identification and expression analysis of a novel splice variant of human Sprouty1 gene.

Sprouty (SPRY) was first identified in a genetic screen in Drosophila to be an antagonist of fibroblast growth factor (FGF) and epidermal growth factor (EGF) signaling, seemingly by inhibiting the Ras/MAP kinase pathway. During large scale DNA sequencing of the human fetal brain cDNA library, we cloned a novel splice variant of human Sprouty1 gene, and termed it human Sprouty1b (SPRY1b). It has the same deduced protein as Sprouty1a, which has been reported.

Cloning and identification of the human LPAAT-zeta gene, a novel member of the lysophosphatidic acid acyltransferase family.

Lysophosphatidic acid (LPA) is a naturally occurring component of phospholipid and plays a critical role in the regulation of many physiological and pathophysiological processes including cell growth, survival, and pro-angiogenesis. LPA is converted to phosphatidic acid by the action of lysophosphatidic acid acyltransferase (LPAAT). Five members of the LPAAT gene family have been detected in humans to date.

Precursor peptide progastrin(1-80) reduces apoptosis of intestinal epithelial cells and upregulates cytochrome c oxidase Vb levels and synthesis of ATP.

We recently reported that downregulation of gastrin gene expression in colon cancer cells significantly suppresses relative levels of mitochondrial cytochrome c (cyt c) oxidase Vb (Cox Vb) RNA and protein. These unexpected findings suggested the possibility that gastrin gene products [mainly progastrin (PG)] may be directly or indirectly mediating the observed effects in colon cancer cells. Because colon cancer cells do not respond to exogenous PG, we examined the possibility of whether PG regulates Cox Vb expression in gastrin-responsive intestinal epithelial cells (IECs) in vitro.

Molecular cloning and characterization of a novel human J-domain protein gene (HDJ3) from the fetal brain.

The J-domain is believed to be part of a chaperone involved in protein folding. From a fetal brain cDNA library, we isolated a cDNA of 3249 bp encoding a novel human J-domain protein, which was named as HDJ3. The expression pattern of HDJ3 was examined by reverse transcription/polymerase chain reaction, which suggested that the transcripts were highly expressed in human pancreas and selectively expressed in human brain, lung, liver, skeletal muscle and kidney.

Human papillomavirus-related cervical lesions in adolescents: a histologic and morphometric study.

Objective: To evaluate the cytopathic effect of human papillomavirus (HPV) infection in adolescents.

Methods: Cervical biopsies from 100 patients, 50 from adolescents age 14 to 20 and 50 from mature women age 35 to 64, all diagnosed with HPV-related lesions (condylomas), were studied histologically and morphometrically. Fifty were associated with low-grade squamous intraepithelial lesions and 50 with high-grade squamous intraepithelial lesions.

Human CRYL1, a novel enzyme-crystallin overexpressed in liver and kidney and downregulated in 58% of liver cancer tissues from 60 Chinese patients, and four new homologs from other mammalians.

Lambda-crystallin is a composition of lens in rabbit and hare. It contains the putative NAD- or FAD-binding domain, which is named as HCDH domain in 3-hydroxyacyl-CoA dehydrogenase. In our attempt to search for genes differentially expressed between liver cancer tissues and normal tissues, human CRYL1 (crystallin, lambda 1) was identified.

Identification of a novel human DDX40gene, a new member of the DEAH-box protein family.

The DExH/D-box superfamily of RNA helicases seems to play key roles during RNA metabolism, such as pre-mRNA splicing, ribosome biogenesis, and others. We have cloned a new gene of the DEAH-box protein subgroup, designated DDX40 (DEAD/H-box polypeptide 40 gene). DDX40 contains 3656 nucleotides and codes for a putative 779-amino-acid protein.

Control of facial muscle development by MyoR and capsulin.

Members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors control the formation of all skeletal muscles in vertebrates, but little is known of the molecules or mechanisms that confer unique identities to different types of skeletal muscles. MyoR and capsulin are related bHLH transcription factors expressed in specific facial muscle precursors. We show that specific facial muscles are missing in mice lacking both MyoR and capsulin, reflecting the absence of MyoD family gene expression and ablation of the corresponding myogenic lineages.

Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor.

The four MEF2 transcription factors (MEF2A, -B, -C, and -D) regulate differentiation and calcium-dependent gene expression in muscle cells. We generated mice deficient in MEF2A, the predominant Mef2 gene product expressed in post-natal cardiac muscle. Most mice lacking Mef2a died suddenly within the first week of life and exhibited pronounced dilation of the right ventricle, myofibrillar fragmentation, mitochondrial disorganization and activation of a fetal cardiac gene program.

Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.

The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism.

Activation of the MEF2 transcription factor in skeletal muscles from myotonic mice.

Becker syndrome, a recessive nondystrophic myotonia caused by mutations in the chloride channel 1 gene (CLCN1), is characterized by delayed muscle relaxation after contraction. The ADR (arrested development of righting response) mouse is an animal model for Becker syndrome. Skeletal muscles from ADR myotonic animals show an increased number of oxidative fibers with a lack of glycolytic fibers as well as signs of muscle hypertrophy.

Regulation of mitochondrial biogenesis in skeletal muscle by CaMK.

Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis, up-regulation of mitochondrial enzymes involved in fatty acid metabolism and electron transport, and reduced susceptibility to fatigue during repetitive contractions.