Cyclic phosphatidic acid decreases proliferation and survival of colon cancer cells by inhibiting peroxisome proliferator-activated receptor γ.

Cyclic phosphatidic acid (cPA), a structural analog of lysophosphatidic acid (LPA), is one of the simplest phospholipids found in every cell type. cPA is a specific, high-affinity antagonist of peroxisome proliferator-activated receptor gamma (PPARγ); however, the molecular mechanism by which cPA inhibits cellular proliferation remains to be clarified. In this study, we found that inhibition of PPARγ prevents proliferation of human colon cancer HT-29 cells.

Saccade adaptation as a model of learning in voluntary movements.

Motor learning ensures the accuracy of our daily movements. However, we know relatively little about its mechanisms, particularly for voluntary movements. Saccadic eye movements serve to bring the image of a visual target precisely onto the fovea.

Learning signals from the superior colliculus for adaptation of saccadic eye movements in the monkey.

Vital to motor learning is information about movement error. Using this information, the brain creates neural learning signals that instruct a plasticity mechanism to produce appropriate behavioral learning. Little is known, however, about brain structures that generate learning signals for voluntary movements.

Role of glycinergic inhibition in shaping activity of saccadic burst neurons.

The immediate premotor signals for saccades are created at the level of medium-lead burst neurons (MLBNs). During fixations, MLBNs receive tonic inhibition from omnipause neurons (OPNs), which use glycine as a neurotransmitter. To elucidate the role of this inhibition, we studied discharge patterns of horizontal MLBNs following iontophoretic application of strychnine, a glycine-receptor antagonist, in alert cats.

c-Jun NH(2)-terminal kinase mediates leptin-stimulated androgen-independent prostate cancer cell proliferation via signal transducer and activator of transcription 3 and Akt.

Obesity is associated with advanced prostate cancer. Here we demonstrate that in mouse prostate cancer TRAMP-C1 cells epididymal fat extracts from high-fat diet-fed obese mice stimulate androgen-independent cell growth more significantly than those from low-fat diet-fed lean mice or genetically obese leptin-deficient ob/ob mice in correlation with leptin concentrations. This result suggests that obesity promotes androgen-independent prostate cancer cell growth via adipose leptin.

Premotor inhibitory neurons carry signals related to saccade adaptation in the monkey.

Cerebellar output changes during motor learning. How these changes cause alterations of motoneuron activity and movement remains an unresolved question for voluntary movements. To answer this question, we examined premotor neurons for saccadic eye movement.

Functional analysis of human mutations in homeodomain transcription factor PITX3.

Background: The homeodomain-containing transcription factor PITX3 was shown to be essential for normal eye development in vertebrates. Human patients with point mutations in PITX3 demonstrate congenital cataracts along with anterior segment defects in some cases when one allele is affected and microphthalmia with brain malformations when both copies are mutated. The functional consequences of these human mutations remain unknown.

Role of STAT3 in liver regeneration: survival, DNA synthesis, inflammatory reaction and liver mass recovery.

The hepatoprotective effect of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) has been well documented. However, reports on the role of IL-6/STAT3 in liver regeneration are conflicting probably due to the fact that the model of Stat3 knockout mice were complicated with obesity and fatty liver, which may cause some secondary effects on liver regeneration. To study the direct role of STAT3 and to circumvent the problems of obesity and fatty liver in liver regeneration, we generated conditional STAT3 knockout in the liver (L-Stat3(-/-)) using a transthyretin-driven Cre-lox method.

Microstimulation of the midbrain tegmentum creates learning signals for saccade adaptation.

Error signals are vital to motor learning. However, we know little about pathways that transmit error signals for learning in voluntary movements. Here we show that microstimulation of the midbrain tegmentum can induce learning in saccadic eye movements in monkeys.

Glycinergic inputs cause the pause of pontine omnipause neurons during saccades.

Pontine omnipause neurons (OPNs) are inhibitory neurons projecting to saccade-related premotor burst neurons. OPNs exhibit sustained discharge during fixations and cease firing before and during saccades. The pause in OPN discharge releases the burst neurons from tonic inhibition, resulting in generation of saccadic eye movements.

The location of brainstem neurons with bilateral projections to the motor nuclei of jaw openers in the cat.

Symmetrical motor output is the rule in the masticatory system. We examined morphologically how this functional symmetry might be reflected in the organization of premotor neurons that could mediate excitation of jaw-opener motoneurons. Premotor neurons projecting bilaterally to jaw-opener motoneurons by way of axon collaterals were identified by retrograde dual-labeling with cholera toxin B-conjugated fluorescein isothiocyanate (CTb-FITC) and tetramethylrhodamine (TMR).

Adiponectin as a growth inhibitor in prostate cancer cells.

Prostate cancer is associated with obesity. However, the molecular basis of this association is not well known. Adiponectin is a major adipose cytokine that decreases in circulation in obesity and ameliorates obesity.

Effect of saccadic amplitude adaptation on subsequent adaptation of saccades in different directions.

We have shown previously that adaptation of horizontal saccades exerts facilitating effects on subsequent adaptation of saccades in the same direction. Now we investigated the effect on saccades in different directions. A series of three alternating gain changes was induced by intrasaccadic step (ISS) of the target in two monkeys.

Adiponectin activates c-Jun NH2-terminal kinase and inhibits signal transducer and activator of transcription 3.

Adiponectin, a major adipose cytokine, plays a crucial role in the inhibition of metabolic syndrome by acting on such cell types as muscle cells and hepatocytes. Furthermore, evidence suggests that adiponectin may influence cancer pathogenesis. Adiponectin occurs in non-proteolytic (full-length adiponectin: f-adiponectin) and proteolytic (globular adiponectin: g-adiponectin) forms in various oligomeric states.

BCG directly induces cell cycle arrest in human transitional carcinoma cell lines as a consequence of integrin cross-linking.

Background: Current models of the mechanism by which intravesical BCG induces an anti-tumor effect in urothelial carcinoma propose a secondary cellular immune response as principally responsible. Our group has demonstrated that BCG mediated cross-linking of alpha51 integrin receptors present on the tumor surface elicits a complex biologic response involving AP1 and NF-kappaB signaling as well as the transactivation of immediate early genes. This study evaluated the direct biologic effect of cross-linking alpha5beta1 integrin on cell cycle progression and apoptosis in two human urothelial carcinoma cell lines.

2-arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion.

Endocannabinoids have been implicated in cancer. Increasing endogenous 2-arachidonoylglycerol (2-AG) by blocking its metabolism inhibits invasion of androgen-independent prostate cancer (PC-3 and DU-145) cells. Noladin ether (a stable 2-AG analog) and exogenous CB1 receptor agonists possess similar effects.

Autocrine over expression of fibronectin by human transitional carcinoma cells impairs bacillus Calmette-Guerin adherence and signaling.

Purpose: Bacillus Calmette-Guerin (BCG) binds to the tumor cell as a result of mycobacterial receptors for fibronectin (FN). Cell surface bound FN serves as a bridge through which BCG attaches to the tumor cell. Despite the importance of FN studies have demonstrated an idiosyncratic decrease in BCG adherence in response to exogenous FN.

Memory of learning facilitates saccadic adaptation in the monkey.

A motor learning mechanism called saccadic adaptation ensures accuracy of saccades throughout life despite growth, aging, and some pathologies of the oculomotor plant or nervous system. The present study investigates effects of preceding adaptation on the speed of subsequent adaptation during single experiments. Adaptive changes in gain (movement size divided by target eccentricity) were induced by intrasaccadic step (ISS) of the target.

Vertical eye movement-related type II neurons with downward on-directions in the vestibular nucleus in alert cats.

The vestibular nuclei and the interstitial nucleus of Cajal (INC) have been regarded as key elements of the velocity-to-position integrator for vertical eye movements. This paper reports a class of type II vestibular neurons that receives input from the INC and carries vertical eye movement signals that appear to represent an intermediate stage of the integration process. Extracellular recordings were made from neurons in and near the vestibular nuclei in alert cats.

Endothelial cells require STAT3 for protection against endotoxin-induced inflammation.

Endothelial cells (ECs) are believed to be an important component in the protection from lipopolysaccharide (LPS)-induced endotoxic shock. However, the cellular and molecular mechanism is not well defined. Here, we report that signal transducer and activator of transcription (STAT) 3 is an essential regulator of the antiinflammatory function of ECs in systemic immunity.

Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age.

Cytokines and inflammation have been implicated in the pathogenesis of heart failure. For example, IL-6 family cytokines and the gp130 receptor play important roles in cardiac myocyte survival and hypertrophy. Signal transducer and activator of transcription 3 (STAT3) is a major signaling protein that is activated through gp130.

Androgen dependent regulation of bacillus Calmette-Guerin induced interleukin-6 expression in human transitional carcinoma cell lines.

Purpose: Autocrine expression of interleukin (IL)-6 by transitional cell carcinoma (TCC) in response to bacillus Calmette-Guerin (BCG) may have an important role in promoting BCG adherence to TCC and consequently in BCG treatment efficacy. IL-6 expression in response to BCG requires nuclear factor (NF)-kappaB mediated signal transduction. We evaluated the influence of androgens on BCG induced, NF-kappaB mediated IL-6 expression.

Prostate cancer cell-adipocyte interaction: leptin mediates androgen-independent prostate cancer cell proliferation through c-Jun NH2-terminal kinase.

Prostate cancer is one of the leading causes of death among men in the United States, and acquisition of hormone resistance (androgen independence) by cancer cells is a fatal event during the natural history of prostate cancer. Obesity is another serious health problem and has been shown to be associated with prostate cancer. However, little is known about the molecular basis of this association.

Contribution of GABAergic inhibition to the responses of secondary vestibular neurons to head rotation in the rat.

To assess the contribution of GABAA receptor-mediated inputs in control of vestibular responses of secondary vestibular neurons, we examined the effects of the GABAA receptor antagonists, bicuculline and picrotoxin, on these neurons in anesthetized rats. Horizontal canal-related secondary vestibular neurons were identified by their monosynaptic excitation from the ipsilateral vestibular nerve and by the modulation of their firing rate for head rotation. Responses to sinusoidal head rotation were recorded before and during iontophoretic application of the drugs.