3,126 research outputs found
Insulin-Like Growth Factor II (IGF-II) Is More Potent Than IGF-I in Stimulating Cortisol Secretion from Cultured Bovine Adrenocortical Cells: Interaction with the IGF-I Receptor and IGF-Binding Proteins
Although the stimulating effect of insulin-like growth factor I (IGF-I) on adrenal steroidogenesis has been well established, the role of IGF-II in the adult adrenal gland remains unknown. We, therefore, investigated the effect of recombinant human IGF-II on cortisol and cAMP synthesis from adult bovine adrenocortical cells. IGF-II, time and dose dependently, stimulated basal cortisol secretion maximally 3-fold. In combination with ACTH, IGF-II (13 nM) synergistically increased cortisol secretion from 1-fold (10(-8) M ACTH) to 28-fold of untreated control levels. In contrast, IGF-I at equimolar concentrations did not show an effect on basal cortisol secretion, and in combination with ACTH elicited a significant weaker stimulatory effect than IGF-II (22-fold increase). The synergistic effect of IGF-II on ACTH-promoted cortisol secretion was paralleled by accumulation of cAMP in the culture medium. Although both IGF receptors are present in adult bovine adrenocortical cells, the effect of IGF-II seems to be mediated through interaction with the IGF-I receptor, as [Arg54,55]IGF-II, which only binds to the IGF-I receptor, was equipotent to native IGF-II, whereas [Leu27]IGF-II, which preferentially binds to the type II IGF receptor, did not show any effect. By Western ligand blotting, four different molecular forms of IGF-binding proteins (IGFBPs) were identified in conditioned medium of bovine adrenocortical cells with apparent molecular masses of 39-44, 34, 29, and 24 kilodaltons. ACTH treatment increased the abundance of all binding proteins, on the average, 2.3-fold, except for the 29-kDa band, which was predominantly induced 6.8-fold. Additionally, [des1-3]IGF-I, a truncated IGF variant that exhibits only minimal binding to IGFBPs, was significant more potent than IGF-I and elicited the same maximum stimulatory effect on cortisol secretion as IGF-II and [des1-6]IGF-II. In conclusion, these results demonstrate that 1) IGF-II stimulates basal as well as ACTH-induced cortisol secretion from bovine adrenocortical cells more potently than IGF-I; 2) this effect is mediated through interaction of IGF-II with the IGF-I receptor; 3) bovine adrenocortical cells synthesize various IGFBPs that are induced differentially by ACTH; and 4) IGFBPs apparently play a modulatory role in IGF-induced stimulation of adrenal steroidogenesis. Therefore, bovine adult adrenocortical cells provide a useful tissue culture model in which the interactions among locally produced IGFs, IGFBPs, and the IGF-I receptor can be evaluated
Cardiovascular Benefits of GLP-1-BasedTherapies in Patients with Diabetes Mellitus Type 2: Effects on Endothelial and Vascular Dysfunction beyond Glycemic Control
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors
Reversible Tuning of Collinear versus Chiral Magnetic Order by Chemical Stimulus
The Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction mediates collinear
magnetic interactions via the conduction electrons of a non-magnetic spacer,
resulting in a ferro- or antiferromagnetic magnetization in magnetic
multilayers. The resulting spin-polarized charge transport effects have found
numerous applications. Recently it has been discovered that heavy non-magnetic
spacers are able to mediate an indirect magnetic coupling that is non-collinear
and chiral. This Dzyaloshinskii-Moriya-enhanced RKKY (DME-RKKY) interaction
causes the emergence of a variety of interesting magnetic structures, such as
skyrmions and spin spirals. Applications using these magnetic quasi-particles
require a thorough understanding and fine-tuning of the balance between the
Dzyaloshinskii-Moriya interaction and other magnetic interactions, e.g., the
exchange interaction and magnetic anisotropy contributions. Here, we show by
spin-polarized scanning tunneling microscopy that the spin structure of
manganese oxide chains on Ir(001) can reproducibly be switched from chiral to
collinear antiferromagnetic interchain interactions by increasing the oxidation
state of MnO while the reverse process can be induced by thermal reduction.
The underlying structural change is revealed by low-energy electron diffraction
intensity data (LEED-IV) analysis. Density functional theory calculations
suggest that the magnetic transition may be caused by a significant increase of
the Heisenberg exchange upon oxidation.Comment: 6 pages, 3 figure
Photoassociation and coherent transient dynamics in the interaction of ultracold rubidium atoms with shaped femtosecond pulses - I. Experiment
We experimentally investigate various processes present in the
photoassociative interaction of an ultracold atomic sample with shaped
femtosecond laser pulses. We demonstrate the photoassociation of pairs of
rubidium atoms into electronically excited, bound molecular states using
spectrally cut femtosecond laser pulses tuned below the rubidium D1 or D2
asymptote. Time-resolved pump-probe spectra reveal coherent oscillations of the
molecular formation rate, which are due to coherent transient dynamics in the
electronic excitation. The oscillation frequency corresponds to the detun-ing
of the spectral cut position to the asymptotic transition frequency of the
rubidium D1 or D2 lines, respectively. Measurements of the molecular
photoassociation signal as a function of the pulse energy reveal a non-linear
dependence and indicate a non-perturbative excitation process. Chirping the
association laser pulse allowed us to change the phase of the coherent
transients. Furthermore, a signature for molecules in the electronic ground
state is found, which is attributed to molecule formation by femtosecond
photoassociation followed by spontaneous decay. In a subsequent article [A.
Merli et al., submitted] quantum mechanical calculations are presented, which
compare well with the experimental data and reveal further details about the
observed coherent transient dynamics
Coherent control with shaped femtosecond laser pulses applied to ultracold molecules
We report on coherent control of excitation processes of translationally
ultracold rubidium dimers in a magneto-optical trap by using shaped femtosecond
laser pulses. Evolution strategies are applied in a feedback loop in order to
optimize the photoexcitation of the Rb2 molecules, which subsequently undergo
ionization or fragmentation. A superior performance of the resulting pulses
compared to unshaped pulses of the same pulse energy is obtained by
distributing the energy among specific spectral components. The demonstration
of coherent control to ultracold ensembles opens a path to actively influence
fundamental photo-induced processes in molecular quantum gases
Increased cytoplasmatic expression of cancer immune surveillance receptor CD1d in anaplastic thyroid carcinomas
Background Anaplastic thyroid carcinomas are associated with rapid tumor growth, short survival time and without any promising therapy to improve the poor prognosis. In this study, expression of immunoregulative receptor CD1d and lymphocyte infiltration in different thyroid tumors as well as in healthy tissue were analyzed in order to find new targets for an immunotherapeutic approach. Methods CD1d immunohistochemistry was performed in samples of 18 anaplastic, 17 follicular, 27 papillary, and 4 medullary thyroid carcinomas as well as in 19 specimens from normal thyroid tissue and additionally in 10 samples of sarcoma, seven malignant melanoma and three spindle-cell lung carcinoma. Furthermore, thyroid samples were stained with antibodies against CD3, CD20, CD56, CD68, and LCA in order to analyze lymphocyte infiltration. Results For the first time CD1d receptor expression on normal thyroid tissue could be demonstrated. Moreover, anaplastic thyroid carcinomas showed significantly higher expression levels compared to other thyroid samples. Most astonishingly, CD1d expression disappeared from the cellular surface and was detected rather in the cytoplasm of anaplastic thyroid carcinoma cells. In addition, histologically similar tumors to anaplastic carcinoma like sarcoma and malignant melanoma revealed distinct CD1d staining patterns. Furthermore, infiltration of T cells, B cells, and macrophages in anaplastic thyroid carcinomas was different when compared to normal thyroid tissue and all other thyroid carcinomas. Conclusions Anaplastic thyroid carcinomas show significantly higher expression of CD1d, a receptor for NKT cells, which are subject of several anticancer therapy studies. These results may offer a novel approach to explore immunotherapeutic treatment options
Competence of graph convolutional network in anti-money laundering in Bitcoin Blockchain
Graph networks are extensively used as an essential framework to analyse the interconnections between transactions and capture illicit behaviour in Bitcoin blockchain. Due to the complexity of Bitcoin transaction graph, the prediction of illicit transactions has become a challenging problem to unveil illicit services over the network. Graph Convolutional Network, a graph neural network based spectral approach, has recently emerged and gained much attention regarding graph-structured data. Previous research has highlighted the degraded performance of the latter approach to predict illicit transactions using, a Bitcoin transaction graph, so-called Elliptic data derived from Bitcoin blockchain. Motivated by the previous work, we seek to explore graph convolutions in a novel way. For this purpose, we present a novel approach that is modelled using the existing Graph Convolutional Network intertwined with linear layers. Concisely, we concatenate node embeddings obtained from graph convolutional layers with a single hidden layer derived from the linear transformation of the node feature matrix and followed by Multi-layer Perceptron. Our approach is evaluated using Elliptic data, wherein efficient accuracy is yielded. The proposed approach outperforms the original work of same data set
Strange matter in rotating compact stars
We have constructed equations of state involving various exotic forms of
matter with large strangeness fraction such as hyperon matter, Bose-Einstein
condensates of antikaons and strange quark matter. First order phase
transitions from hadronic to antikaon condensed and quark matter are considered
here. The hadronic phase is described by the relativistic field theoretical
model. Later those equations of state are exploited to investigate models of
uniformly rotating compact stars. The effect of rotation on the third family
branch for the equation of state involving only antikaon condensates is
investigated. We also discuss the back bending phenomenon due to a first order
phase transition from condensed to quark matter.Comment: 8 pages, 4 figures; Plenary talk delivered at Strangeness in Quark
Matter (SQM) 2004 held in Cape Town, South Africa from 15-20 September;
Accepted for publication in the proceedings in Journal of Physics
Robustness of the charge-ordered phases in against photoexcitation
We present a time-resolved angle-resolved photoelectron spectroscopy study of IrTe2, which undergoes two first-order structural and charge-ordered phase transitions on cooling below 270 K and below 180 K. The possibility of inducing a phase transition by photoexcitation with near-infrared femtosecond pulses is investigated in the charge-ordered phases. We observe changes of the spectral function occurring within a few hundreds of femtoseconds and persisting up to several picoseconds, which we interpret as a partial photoinduced phase transition (PIPT). The necessary time for photoinducing these spectral changes increases with increasing photoexcitation density and reaches time scales longer than the rise time of the transient electronic temperature. We conclude that the PIPT is driven by a transient increase of the lattice temperature following the energy transfer from the electrons. However, the photoinduced changes of the spectral function are small, which indicates that the low- temperature phase is particularly robust against photoexcitation. We suggest that the system might be trapped in an out-of-equilibrium state, for which only a partial structural transition is achieved
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