The Role of Specific Mitogen-Activated Protein Kinase Signaling Cascades in the Regulation of Steroidogenesis

Mitogen-activated protein kinases (MAPKs) comprise a family of serine/threonine kinases that are activated by a large variety of extracellular stimuli and play integral roles in controlling many cellular processes, from the cell surface to the nucleus. The MAPK family includes four distinct MAPK cascades, that is, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, c-Jun N-terminal kinase or stress-activated protein kinase, and ERK5. These MAPKs are essentially operated through three-tiered consecutive phosphorylation events catalyzed by a MAPK kinase kinase, a MAPK kinase, and a MAPK. MAPKs lie in protein kinase cascades. The MAPK signaling pathways have been demonstrated to be associated with events regulating the expression of the steroidogenic acute regulatory protein (StAR) and steroidogenesis in steroidogenic tissues. However, it has become clear that the regulation of MAPK-dependent StAR expression and steroid synthesis is a complex process and is context dependent. This paper summarizes the current level of understanding concerning the roles of the MAPK signaling cascades in the regulation of StAR expression and steroidogenesis in different steroidogenic cell models

Can we predict reactivity for aromatic nucleophilic substitution with [ 18 F]fluoride ion?

The correlation between the 13 C‐NMR chemical shift of the aromatic ring carbon bearing the leaving group and the yield of nucleophilic aromatic displacement with no‐carrier‐added [ 18 F]fluoride ion was evaluated. In comparison of structurally analogous compounds (fluoro, nitro and trimethylammonium substituted benzaldehydes, benzophenones and benzonitriles), the 13 C‐NMR chemical shift of the reactive aryl ring carbon correlated quite well with the [ 18 F]fluorination yield (r 2 =0.87) for most but not all ring structures. Compounds with trimethylammonium leaving groups or methyl ring substituents were found to not fit the proposed correlation. Kinetic studies indicated clearly different rates of reaction for these compounds, with much higher than expected reactivity for the ccompounds with the cationic leaving group. Competition experiments suggest that low reactivity of methyl‐substituted rings may be due to conversion of [ 18 F]fluoride to an unreactive form. Our results indicate that the correlation between [ 18 F]fluorination yields for nucleophilic aromatic substitution reactions and the 13 C NMR chemical shift of the aryl ring carbon bearing the leaving group is applicable to numerous structurally analogous compounds, but cannot be simply generalized to aromatic rings with different leaving groups or ring substituents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90183/1/2580330702_ftp.pd

Extreme thrombocytosis in traumatic amputee and role of thromboembolism prophylaxis: a case report

Platelets are the smallest blood component produced in the bone marrow that plays a fundamental role in the blood clotting process. A normal platelet count applicable to all adults is 150 to 400×109/l. Thrombocytosis develops when the platelet count exceeds 450×109/l. Thrombocytosis is classified into primary thrombocytosis and secondary (or extreme) thrombocytosis. Primary thrombocytosis is a chronic myeloproliferative disorder in which sustained megakaryocyte proliferation leads to an increase in the number of circulating platelets. Extreme thrombocytosis or reactive thrombocytosis, is defined as abnormally high platelet count in the absence of chronic myeloproliferative disease, secondary to an underlying events, disease, or the use of certain medications. Causes of reactive thrombocytosis include acute blood loss, acute infection, amputation, iron deficiency, asplenia, cancer, chronic inflammatory or infectious diseases. Secondary thrombocytosis resolves when the underlying event is managed. Extreme thrombocytosis may result in thromboembolic episode such as mesenteric vein thrombosis, pulmonary embolism and acute myocardial infarction. In patients who survive after trauma the platelet count displays a bimodal response with an initial decrease below baseline values, followed by an increase above the normal range after 1 week. We report a similar experience of a trauma patient with reactive thrombocytosis and discussion on importance of thromboprophylaxis

Interference of stochastic resonances: Splitting of Kramers' rate

We consider the escape of particles located in the middle well of a symmetric triple well potential driven sinusoidally by two forces such that the potential wells roll as in stochastic resonance and the height of the potential barrier oscillates symmetrically about a mean as in resonant activation. It has been shown that depending on their phase difference the application of these two synchronized signals may lead to a splitting of time averaged Kramers' escape rate and a preferential product distribution in a parallel chemical reaction in the steady state

Anisotropic Diffusion in Driven Convection Arrays

We numerically investigate the transport of a Brownian colloidal particle in a square array of planar counter-rotating convection rolls at high Peclet numbers. We show that an external force produces huge excess peaks of the particle's diffusion constant with a height that depends on the force orientation and intensity. In sharp contrast, the particle's mobility is isotropic and force independent. We relate such a nonlinear response of the system to the advection properties of the laminar flow in the suspension fluid

Control of NFAT Isoform Activation and NFAT-Dependent Gene Expression through Two Coincident and Spatially Segregated Intracellular Ca 2+ Signals

© 2016 The Author(s) Excitation-transcription coupling, linking stimulation at the cell surface to changes in nuclear gene expression, is conserved throughout eukaryotes. How closely related coexpressed transcription factors are differentially activated remains unclear. Here, we show that two Ca2+-dependent transcription factor isoforms, NFAT1 and NFAT4, require distinct sub-cellular InsP3 and Ca2+ signals for physiologically sustained activation. NFAT1 is stimulated by sub-plasmalemmal Ca2+ microdomains, whereas NFAT4 additionally requires Ca2+ mobilization from the inner nuclear envelope by nuclear InsP3 receptors. NFAT1 is rephosphorylated (deactivated) more slowly than NFAT4 in both cytoplasm and nucleus, enabling a more prolonged activation phase. Oscillations in cytoplasmic Ca2+, long considered the physiological form of Ca2+ signaling, play no role in activating either NFAT protein. Instead, effective sustained physiological activation of NFAT4 is tightly linked to oscillations in nuclear Ca2+. Our results show how gene expression can be controlled by coincident yet geographically distinct Ca2+ signals, generated by a freely diffusible InsP3 message

Quantum oscillator on complex projective space (Lobachewski space) in constant magnetic field and the issue of generic boundary conditions

We perform a 1-parameter family of self-adjoint extensions characterized by the parameter $\omega_0$. This allows us to get generic boundary conditions for the quantum oscillator on $N$ dimensional complex projective space($\mathbb{C}P^N$) and on its non-compact version i.e., Lobachewski space($\mathcal L_N$) in presence of constant magnetic field. As a result, we get a family of energy spectrums for the oscillator. In our formulation the already known result of this oscillator is also belong to the family. We have also obtained energy spectrum which preserve all the symmetry (full hidden symmetry and rotational symmetry) of the oscillator. The method of self-adjoint extensions have been discussed for conic oscillator in presence of constant magnetic field also.Comment: Accepted in Journal of Physics

Enhanced motility in a binary mixture of active nano/microswimmers

It is often desirable to enhance the motility of active nano- or microscale swimmers such as, e.g., self-propelled Janus particles as agents of chemical reactions or weak sperm cells for better chances of successful fertilization. Here we tackle this problem based on the idea that motility can be transferred from a more active guest species to a less active host species. We performed numerical simulations of motility transfer in two typical cases, namely for interacting particles with weak inertia effect, by analyzing their velocity distributions, and for interacting overdamped particles, by studying their effusion rate. In both cases we detected motility transfer with a motility enhancement of the host species of up to a factor of four. This technique of motility enhancement can find applications in chemistry, biology and medicine.Comment: 10 page

Kinetics of self-induced aggregation of Brownian particles: non-Markovian and non-Gaussian features

In this paper we have studied a model for self-induced aggregation in Brownian particle incorporating the non-Markovian and non-Gaussian character of the associated random noise process. In this model the time evolution of each individual is guided by an over-damped Langevin equation of motion with a non-local drift resulting from the local unbalance distributions of the other individuals. Our simulation result shows that colored nose can induce the cluster formation even at large noise strength. Another observation is that critical noise strength grows very rapidly with increase of noise correlation time for Gaussian noise than non Gaussian one. However, at long time limit the cluster number in aggregation process decreases with time following a power law. The exponent in the power law increases remarkable for switching from Markovian to non Markovian noise process

Oxidation of substituted 4-fluorobenzaldehydes: Application to the no-carrier-added syntheses of 4-[18F]fluoroguaiacol and 4-[18F]fluorocatechol

The synthesis of 4-[18F]fluoroguaiacol (4-[18F]fluoro-2-methoxyphenol) has been achieved in no-carrier-added form starting from 2-methoxy-4-nitrobenzaldehyde, using nucleophilic aromatic substitution by [18F]fluoride followed by Baeyer-Villiger oxidation of the benzaldehyde to the phenol. Demethylation with boron tribromide gave 4-[18F]fluorocatechol (1,2-dihydroxy-4-[18F]fluorobenzene) with an overall yield of 18-28% (EOB) in less than 2 h synthesis time. The fluorine-18 labeled intermediates and products were identical to standards of 4-fluoroguaiacol and 4-fluorocatechol prepared by the same methods. This represents a new approach to the synthesis of fluorinated phenols in fluorine-19 and fluorine-18 forms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29638/1/0000727.pd