Expression profile and function of secretogranin V, and its effects on the malignant behavior of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the most aggressive cancers with a poor prognosis. Global expression profiling was conducted on primary ESCC tissues with distant metastases. We investigated the identification of secretogranin V (SCG5) as a promising biomarker for the detection and assessment of ESCC.

KCNQ4 potassium channel subunit deletion leads to exaggerated acoustic startle reflex in mice.

The potassium voltage-gated channel subfamily Q member 4 (KCNQ4) subunit forms channels responsible for M-current, a muscarine-sensitive potassium current regulating neuronal excitability. In contrast to other KCNQ subunits, its expression is restricted to the cochlear outer hair cells, the auditory brainstem and other brainstem nuclei in a great overlap with structures involved in startle reflex. We aimed to show whether startle reflexis affected by the loss of KCNQ4 subunit and whether these alterations are similar to the ones caused by brainstem hyperexcitability.

Modulation of motor behavior by the mesencephalic locomotor region.

The mesencephalic locomotor region (MLR) serves as an interface between higher-order motor systems and lower motor neurons. The excitatory module of the MLR is composed of the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CnF), and their activation has been proposed to elicit different modalities of movement. However, how the differences in connectivity and physiological properties explain their contributions to motor activity is not well known.

Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit.

The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to the regulation of the sleep-wakefulness cycle. The M-current is a voltage-gated potassium current modulated mainly by cholinergic signaling. KCNQ subunits ensemble into ion channels responsible for the M-current.

Topographical Organization of M-Current on Dorsal and Median Raphe Serotonergic Neurons.

Dorsal and median raphe nuclei (DR and MR, respectively) are members of the reticular activating system and play important role in the regulation of the sleep-wakefulness cycle, movement, and affective states. M-current is a voltage-gated potassium current under the control of neuromodulatory mechanisms setting neuronal excitability. Our goal was to determine the proportion of DR and MR serotonergic neurons possessing M-current and whether they are organized topographically.

Orexinergic actions modify occurrence of slow inward currents on neurons in the pedunculopontine nucleus.

Orexins are neuromodulatory peptides of the lateral hypothalamus which regulate homeostatic mechanisms including sleep-wakefulness cycles. Orexinergic actions stabilize wakefulness by acting on the nuclei of the reticular activating system, including the pedunculopontine nucleus. Orexin application to pedunculopontine neurons produces a noisy tonic inward current and an increase in the frequency and amplitudes of excitatory postsynaptic currents.

Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus.

The pedunculopontine nucleus (PPN) is a part of the reticular activating system which is composed of cholinergic, glutamatergic and GABAergic neurons. Early electrophysiological studies characterized and grouped PPN neurons based on certain functional properties (i.e.

Liver-specific deletion of 3-hydroxy-3-methylglutaryl coenzyme A reductase causes hepatic steatosis and death.

Objective: 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) catalyzes the rate-limiting step in cholesterol biosynthesis and has proven to be an effective target of lipid-lowering drugs, statins. The aim of this study was to understand the role of hepatic HMGCR in vivo.

Methods And Results: To disrupt the HMGCR gene in liver, we generated mice homozygous for a floxed HMGCR allele and heterozygous for a transgene encoding Cre recombinase under the control of the albumin promoter (liver-specific HMGCR knockout mice).

Molecular analysis of a novel LCAT mutation (Gly179 → Arg) found in a patient with complete LCAT deficiency.

Lecithin-cholesterol acyltransferase (LCAT) is an important enzyme involved in the esterification of cholesterol. Here, we report a novel point mutation in the LCAT gene of a 63-year-old female with characteristics of classic familial LCAT deficiency. The patient's clinical manifestations included corneal opacity, mild anemia, mild proteinuria and normal renal function.

Depot-specific expression of lipolytic genes in human adipose tissues--association among CES1 expression, triglyceride lipase activity and adiposity.

Aim: Adipocyte lipolysis is mediated by a family of triglyceride (TG) lipases consisting of hormone-sensitive lipase (LIPE), adipose triglyceride lipase (PNPLA2) and carboxylesterase 1 (CES1); however, little is known about the relationship between the expression of each gene in different depots and TG lipase activity or obesity.

Method: We measured both mRNA expression levels of the lipolytic enzymes (LIPE, PNPLA2 and CES1) and TG lipase activities of biopsy samples obtained from subcutaneous, omental and mesenteric adipose tissues of 34 patients who underwent abdominal surgery. The results were correlated with clinical parameters: adiposity measures, parameters for insulin resistance and plasma lipid levels.

A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle.

Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e.

Large scale replication analysis of loci associated with lipid concentrations in a Japanese population.

Background: Recent genome wide association studies discovered seven novel loci that influence plasma concentrations of triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in Europeans. To date, large scale replication studies using populations with known differences in genome-wide linkage disequilibrium (LD) pattern have not been undertaken.

Methods: To address this issue, we tested associations between single nucleotide polymorphisms (SNPs) within the seven novel loci and plasma lipid profiles in 21 010 Japanese individuals.