Vasoactive intestinal polypeptide (VIP) inhibits prostaglandin-F2α-induced activity of the rabbit myometrium

Seven female rabbits had myometrial autografts transplanted into ear-chambers. The electrical activity of the graft was recorded and mechanical activity observed. Vasoactive intestinal polypeptide (VIP) dose-dependently inhibited myometrial activity induced by prostaglandin-F_2α. This evidence and the occurrence of “VIPergic” nerve fibres, which seem to innervate the myometrial cells, suggest that VIP may play a physiological role in the local control of the myometrial activity.     

Erratum

Detergent solubilized bovine milk fat globule membrane material studied by crossed immunoelectrophoresis combined with histochemical techniques revealed four major protein complexes. All four were found to bind to concanavalin A and three were identified as sialoglycoproteins. Xanthine oxidase activity was associated with the non-sialoglycoprotein precipitate. Immunoabsorption with intact milk fat globules showed an internal location of the xanthine oxidase, whereas the three other main proteins plus Mg²⁺-ATPase and 5′-nucleotidase were disposed on the outer membrane surface. The major proteins from milk fat globule membrane and membrane material isolated from skim milk showed immunochemical identity.     

Brain-specific proteins in the occipital cortex of rats housed in enriched and impoverished environments

The occipital cortex was dissected from the brain of rats housed in either enriched or impoverished environment for four weeks. In environmentally enriched rats the weight of occipital cortex was found to be increased 5.7%, compared to environmentally improverished rats, and the amount of protein was increased 6.0%. The amount of six nervous system-specific proteins was measured by crossed immunoelectrophoresis. Synaptin increased 4.7%, D3 increased 8.3%, and D1 increased 9.6%, whereas D2 was not significantly increased. Compared to D2, D3 and D1 were still increased significantly, although all were present in synaptosomal membrane fractions. The protein S-100 was increased 3.4% and the neuronal protein 14-3-2 was increased 12.2% for the cathodal component whereas the anodal component was not increased. The results were interpreted as representing delayed development of environment-dependent neurons in the environmentally impovershed rats.     

Tooth impact rate in the song of a shorthorned grasshopper: A parameter carrying specific behavioral information

Summary Receptive females of the gomphocerine grasshopperOmocestus viridulus L. were offered different artificial grasshopper songs in a one- or two-channel test situation. In the computer generated songs the tooth-impact-rate and the amplitude functions of the chirp were varied.The results of the one-channel experiments showed that the grasshoppers preferred signals with normal tooth-impact-rate to signals with half the rate. The amplitude function seems to play a minor role in the recognition process, unless this parameter is changed very radically.The results of the two-channel tests were ambiguous. A third test series was developed to interpret these results. It was found that female grasshoppers once excited by an acceptable signal afterwards responded to former unacceptable signals. Accordingly, if just one of the two signals is able to excite the female, the female may subsequently choose randomly between the signals. If the signals are of different sound levels, the louder is preferred.The shorthorned grasshopper may interpret the tooth-impact-rate as a frequency. It is proposed that the grasshopper may use the four sense cell groups of the ear as a simple sort of a spectral analyzer. These cells are tuned to different frequencies and/or differently tuned.The running Root Mean Square value of a grasshopper signal, its dependence on the applied integration time and its possible relation to perceived energy are reported in an appendix.     

Directed evolution of human T-cell receptors with picomolar affinities by phage display

Peptides derived from almost all proteins, including disease-associated proteins, can be presented on the cell surface as peptide-human leukocyte antigen (pHLA) complexes. T cells specifically recognize pHLA with their clonally rearranged T-cell receptors (TCRs), whose natural affinities are limited to approximately 1-100 muM. Here we describe the display of ten different human TCRs on the surface of bacteriophage, stabilized by a nonnative interchain disulfide bond. We report the directed evolution of high-affinity TCRs specific for two different pHLAs: the human T-cell lymphotropic virus type 1 (HTLV-1) tax(11-19) peptide-HLA-A(*)0201 complex and the NY-ESO-1(157-165) tumor-associated peptide antigen-HLA-A(*)0201 complex, with affinities of up to 2.5 nM and 26 pM, respectively, and we demonstrate their high specificity and sensitivity for targeting of cell-surface pHLAs.     

CGH-Explorer: a program for analysis of array-CGH data

SUMMARY: CGH-Explorer is a program for visualization and statistical analysis of microarray-based comparative genomic hybridization (array-CGH) data. The program has preprocessing facilities, tools for graphical exploration of individual arrays or groups of arrays, and tools for statistical identification of regions of amplification and deletion.     

Regulation of EphA 4 kinase activity is required for a subset of axon guidance decisions suggesting a key role for receptor clustering in Eph function

Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic kinase activity. Typically, kinase-activating mutations result in ligand-independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs require kinase activity to signal, but signaling by Ephs in vitro also requires clustering by their membrane bound ephrin ligands. The relative importance of Eph kinase activity and clustering for in vivo functions is unknown. We find that knockin mice expressing a mutant form of EphA4 (EphA4(EE)), whose kinase is constitutively activated in the absence of ephrinB ligands, are deficient in the development of thalamocortical projections and some aspects of central pattern generator rhythmicity. Surprisingly, other functions of EphA4 were regulated normally by EphA4(EE), including midline axon guidance, hindlimb locomotion, in vitro growth cone collapse, and phosphorylation of ephexin1. These results suggest that signaling of Eph RTKs follows a multistep process of induced kinase activity and higher-order clustering different from RTKs responding to soluble ligands.     

Contribution of defects in glucose uptake to carbohydrate intolerance in liver cirrhosis: assessment during physiological glucose and insulin concentrations

It is well established that subjects with liver cirrhosis are insulin resistant, but the contribution of defects in insulin secretion and/or action to glucose intolerance remains unresolved. Healthy individuals and subjects with liver cirrhosis were studied on two occasions: 1) an oral glucose tolerance test was performed, and 2) insulin secretion was inhibited and glucose was infused in a pattern and amount mimicking the systemic delivery rate of glucose after a carbohydrate meal. Insulin was concurrently infused to mimic a healthy postprandial insulin profile. Postabsorptive glucose concentrations were equal (5.36 +/- 0.12 vs. 5.40 +/- 0.25 mmol/l, P = 0.89), despite higher insulin (P < 0.01), C-peptide (P < 0.01), and free fatty acid (P = 0.05) concentrations in cirrhotic than in control subjects. Endogenous glucose release (EGR; 11.50 +/- 0.50 vs. 11.73 +/- 1.00 mumol.kg(-1).min(-1), P = 0.84) and the contribution of gluconeogenesis to EGR (6.60 +/- 0.47 vs. 6.28 +/- 0.64 mumol.kg(-1).min(-1), P = 0.70) were unaltered by cirrhosis. A minimal model recently developed for the oral glucose tolerance test demonstrated an impaired insulin sensitivity index (P < 0.05), whereas the beta-cell response to glucose was unaltered (P = 0.72). During prandial glucose and insulin infusions, the integrated glycemic response was greater in cirrhotic than in control subjects (P < 0.05). EGR decreased promptly and comparably in both groups, but glucose disappearance was insufficient at the prevailing glucose concentration (P < 0.05). Moreover, identical rates of [3-(3)H]glucose infusion produced higher tracer concentrations in cirrhotic than in control subjects (P < 0.05), implying a defect in glucose uptake. In conclusion, carbohydrate intolerance in liver cirrhosis is determined by insulin resistance and the ability of glucose to stimulate insulin secretion. During prandial glucose and insulin concentrations, EGR suppression was unaltered, but glucose uptake was impaired, which demonstrates that intolerance can be ascribed to a defect in glucose uptake, rather than abnormalities in glucose production or beta-cell function. Although insulin secretion ameliorates glucose intolerance, impaired glucose uptake during physiological glucose and insulin concentrations produces marked and sustained hyperglycemia, despite concurrent abnormalities in glucose production or insulin secretion.