Immunoexpression of the relaxin receptor LGR7 in breast and uterine tissues of humans and primates

BACKGROUND: The receptor for the peptide hormone relaxin has recently been identified as the heptahelical G-protein coupled receptor, LGR7. In order to generate molecular tools with which to characterize both in vivo and in vitro expression of this receptor in human and primate tissues, specific monotypic antibodies have been generated and applied to a preliminary analysis of human and primate female reproductive tissues. METHODS: Three peptide sequences were identified from the proposed open reading frame of the cloned LGR7 receptor gene, representing both extracellular and intracellular domains. Two to three rabbits were immunized for each epitope, and the resulting sera subjected to a systematic validation using cultured cells transiently transfected with a receptor-expressing gene construct, or appropriate control constructs. RESULTS: Human and monkey (marmoset, macaque) endometrium showed consistent and specific immunostaining in the stromal cells close to glands. Staining appeared to be more intense in the luteal phase of the cycle. Weak immunostaining was also evident in the endometrial epithelial cells of the marmoset. A myoma in one patient exhibited strong immunostaining in the circumscribing connective tissue. Uterine expression was supported by RT-PCR results from cultured primary endometrial and myometrial cells. Human breast tissue (healthy and tumors) consistently indicated specific immunostaining in the interstitial connective (stromal) tissue within the glands, but not in epithelial or myoepithelial cells, except in some tumors, where a few epithelial and tumor cells also showed weak epitope expression. CONCLUSIONS: Using validated monotypic antibodies recognizing different epitopes of the LGR7 receptor, and from different immunized animals, and in different primate species, a consistent pattern of LGR7 expression was observed in the stromal (connective tissue) cells of the endometrium and breast, consistent also with the known physiology of the relaxin hormone

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Volume of the human hippocampus and clinical response following electroconvulsive therapy

BACKGROUND: Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. METHODS: Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice. RESULTS: The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 +/- 2.2%, d = 1.5; right unilateral, 1.6 +/- 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 +/- 1.7%, d = 1.8; right unilateral, 2.7 +/- 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Asberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .069). CONCLUSIONS: The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome

Simulation von Bauweisen-Konzepten eines AKE Luftfrachtcontainers und deren Bodenplatte

Um neue Werkstoffe und Bauweisen für Luftfrachtcontainer einsetzen zu können, müssen diese qualifiziert werden. Hierfür stehen entweder Tests oder Simulationen zur Verfügung. Für Luftfrachtcontainer sind empfohlene Tests aus ULD Regulations [3] (ehemals dem IATA ULD Technical Manual [2]) bekannt. Da teilweise der komplette Luftfrachtcontainer als ein Bauteil getestet wird, sind nicht alle geforderten Tests umsetzbar. Eine FEM-Simulation ist hier die kostengünstigere und schnellere Alternative

Relaxin signalling in THP-1 cells uses a novel phosphotyrosine-dependent pathway

The heterodimeric peptide hormone relaxin acts through the novel G-protein coupled receptor LGR7 to elicit the production of cAMP in the human monocyte cell line THP-1. The very small number of receptors on the cell surface, and the lack of response in cell membranes imply the involvement of a cytoplasmic signal amplification process. Here we show that this process comprises a novel and specific tyrosine kinase activity close to the receptor, and involves neither protein kinase A, mitogen-activated protein kinase, nor phosphoinositide-3 kinase activities as major upstream components. Furthermore, this novel involvement of a tyrosine kinase activity is cell-type dependent, being largely absent from LGR7-transfected HEK293T cells, and receptor-dependent; vasoactive intestinal peptide or isoproterenol signalling in the same cells does not require this tyrosine kinase activity. © 2007 Elsevier Ireland Ltd. All rights reserved

Hypotensive effects of positive airway pressure ventilation in heart failure patients with sleep-disordered breathing

Oldenburg O, Bartsch S, Bitter T, et al. Hypotensive effects of positive airway pressure ventilation in heart failure patients with sleep-disordered breathing. Sleep And Breathing. 2012;16(3):753-757.Obstructive sleep apnoea (OSA) as well as central sleep apnoea (CSA) are highly prevalent in heart failure (HF) patients. Positive airway pressure (PAP) therapy is usually intended to treat OSA and CSA. The aim of the present study was to investigate immediate hemodynamic effects of PAP therapy in these patients. In 61 consecutive HF patients (NYHA a parts per thousand yenaEuro parts per thousand II, EF a parts per thousand currency signaEuro parts per thousand 45%) with moderate to severe OSA or CSA (AHI a parts per thousand yenaEuro parts per thousand 15/h) blood pressure (BP) and heart rate (HR) response to PAP therapy initiation was investigated during mask fitting with patients being awake and in supine position. While applying an endexspiratory pressure of 5.8 +/- 0.9 cm H2O, there was a significant decrease in systolic (-8.9 +/- 12.1 mmHg, p < 0.001) and diastolic BP (-5.1 +/- 9.2 mmHg, p < 0.001) without a change in HR (p = n.s.). At least a transient drop in mean arterial pressure a parts per thousand currency sign70 mmHg was seen in 10% of these patients. Logistic regression analysis revealed a significant impact of baseline BP on potential BP drops: lower baseline BP was associated with BP drops. PAP therapy may cause unexpected hypotension especially in patients with low baseline BP as seen in HF patients treated according to current guidelines. Whether these hypotensive effects sustain, cause any harm to the patients and/or is responsible for non-acceptance or non-adherence of PAP therapy needs to be determined