Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner

Adiponectin, an adipocyte-specific secretory protein, is present in serum as three oligomeric complexes. Apart from its roles as an anti-diabetic and anti-atherogenic hormone, adiponectin has been implicated as an important regulator of cell growth and tissue remodeling. Here we show that some of these functions might be mediated by the specific interactions of adiponectin with several important growth factors. Among six different growth factors examined, adiponectin was found to bind with platelet-derived growth factor BB (PDGF-BB), basic fibroblast growth factor (FGF), and heparin-binding epidermal growth factor-like growth factor (HB EGF) with distinct affinities. The bindings of adiponectin with these growth factors are oligomerization-dependent. PDGF-BB bound to the high molecular weight (HMW) and middle molecular weight (MMW) complexes, but not to the low molecular weight (LMW) complex of adiponectin. Basic FGF preferentially interacted with the HMW form, whereas HB EGF bound to all three forms with comparable affinities. These three growth factors did not compete with each other for their bindings to adiponectin, suggesting the involvement of distinct binding sites. The interactions of adiponectin with PDGF-BB, basic FGF, and HB EGF precluded the bindings to their respective membrane receptors and attenuated the DNA synthesis and cell proliferation induced by these growth factors. Small interfering RNA-mediated down-regulation of adiponectin receptors did not affect the suppressive effects of adiponectin on cell proliferation stimulated by these growth factors. These data collectively suggest that the oligomeric complexes of adiponectin can modulate the biological actions of several growth factors by controlling their bioavailability at a pre-receptor level and that this effect might partly account for the anti-atherogenic, anti-angiogenic, and anti-proliferative functions of adiponectin.     

Impedance characterization of a piezoelectric immunosensor. Part I: antibody coating and buffer solution

This study investigated the impedance characteristics of a 5 MHz quartz crystal resonator oscillating in a thickness-shear mode for utilization as a biosensor. An impedance analyzer measured the impedance of the quartz crystal, which determined all mechanical properties of the oscillating quartz and its immediate environment. In this study, the impedance behavior of the oscillating crystal was characterized in air, in potassium phosphate buffer solution, and with immobilization of antibodies using protein-A. The potassium phosphate buffer behaved like a Newtonian liquid. The series resonance frequency shifted down about 900 Hz on contact with the buffer. An immobilized-antibody layer on the quartz surface behaved like a rigid mass when immersed in the buffer solution. The impedance curve following immobilization of antibodies was shifted down in frequency by about 200 Hz compared with its value when the bare crystal was immersed in the buffer solution.     

Metabolite profiling identifies the mycotoxin alternariol in the pathogen Stagonospora nodorum

A recent comparative proteomics study identified the short-chain dehydrogenase (Sch1) as being required for asexual sporulation (Tan et al. Eukaryotic Cell 7:1916–1929, 2008). Metabolite profiling was undertaken on the mutant strains of Stagonospora nodorum lacking the Sch1 gene to help elucidate its role. Gas chromatography-mass spectrometry of the polar metabolites in the Sch1 mutants identified a secondary metabolite at a 200-fold greater concentration than observed in the wild-type strains. Comparative analysis of the secondary metabolite and the mycotoxin alternariol using ESI-MS/MS confirmed the identity of the compound as alternariol. This is the first report to confirm the presence of a mycotoxin in S. nodorum and compelling the field to consider the health implication of this disease.     

Amygdala Perfusion Is Predicted by Its Functional Connectivity with the Ventromedial Prefrontal Cortex and Negative Affect

Background

Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states.

Methods

Here we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects.

Results

BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety.

Conclusions

These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.     

Suppression of cytokine production by supernatants from CD8+ lymphocytes activated by mycobacterial fractions: The role of interleukins 4 and 6

Supernatants derived from CD8⁺ lymphocytes treated with mycobacterial components, or the partially purified carbohydrates from these supernatants, increased the production of IL-4 and IL-6 by mononuclear cells. The addition of anti-IL4 or anti-IL6 antibodies to LPS stimulated MN cells incubated with supernatants from CD8⁺ lymphocytes or carbohydrates resulted in the restoration of other cytokine production by these MN cells. Recombinant IL-4 and IL-6 on their own suppressed the production of IL-1, TNF-, IL-2 and IFN- by mononuclear cells. Such suppression could be reversed with antibodies to IL-4 and IL-6. The addition of rIL-4 and rIL-6 did not increase the suppression of cytokine production induced by suppressor supernatants or carbohydrates. Interleukin 4 decreased the production of IL-6 by MN cells; whilst IL-6 suppressed IL-4 production in a dose dependent manner. Both effects could be reversed with the appropriate antisera. Our results suggest that mycobacteria could evade host immunity by inducing the production of IL-4 and IL-6 by host mononuclear cells. These cytokines, in turn, would suppress the production of other cytokines necessary for effective cellular immunity.Abbreviations IL-1 interleukin 1 - IL-2 interleukin 2 - IL-4 interleukin 4 - IL-6 interleukin 6 - IFN- gamma interferon - TNF- tumour necrosis factor alpha - MN cells mononuclear cells - NAL's non-adherent lymphocytes - LPS lipopolysaccharide - PMA phorbol myristate acetate - RIA radioimmunoassay - ELISA enzyme-linked immunosorbent assay - rIL-4 recombinant interlukin-4 - rIL-6 recombinant interleukin-6 - U/ml units per millilitre - g/ml micrograms per millilitre - ng/ml nanograms per millilitre     

Structure of the Chromatium Sulfur Particle and Its Protein Membrane

Sulfur particles extracted from Chromatium vinosum strain D were found to be bounded by a unique proteinaceous membrane. Ultrastructural examination of the membrane in Epon sections and bovine serum albumin sections and examination of negatively stained, sulfur-free membrane ghosts revealed a monomolecular sheet composed of 2.5-nm globular components. The internal sulfur was found to bind large amounts of a variety of negative stains and to form myelin-like structures upon rupture of the surrounding membrane.