Inositol pyrophosphates and Akt: Is the pancreatic β-cell the exception to the rule?

The inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), is thought to negatively regulate the critical insulin signaling protein Akt/PKB. Knock down of the IP7-generating inositol hexakisphosphate kinase 1 (IP6K1) results in a concomitant increase in signaling through Akt/PKB in all cell types so far examined. Total in vivo knockout of IP6K1 is associated with a phenotype resistant to high-fat diet, due to enhanced Akt/PKB signaling in classic insulin regulated tissues, counteracting insulin resistance. In contrast, we have shown an important positive role for IP6K1 in insulin exocytosis in the pancreatic β-cell. These cells also possess functional insulin receptors and the feedback loop following insulin secretion is a key aspect of their normal function. Thus we examined the effect of silencing IP6K1 on the activation of Akt/PKB in β-cells. Silencing reduced the glucose-stimulated increase in Akt/PKB phosphorylation on T308 and S473. These effects were reproduced with the selective pan-IP6K inhibitor TNP. The likely explanation for IP7 reduction decreasing rather than increasing Akt/PKB phosphorylation is that IP7 is responsible for generating the insulin signal, which is the main source of Akt/PKB activation. In agreement, insulin receptor activation was compromised in TNP treated cells. To test whether the mechanism of IP7 inhibition of Akt/PKB still exists in β-cells, we treated them at basal glucose with an insulin concentration equivalent to that reached during glucose stimulation. TNP potentiated the Akt/PKB phosphorylation of T308 induced by exogenous insulin. Thus, the IP7 regulation of β-cell Akt/PKB is determined by two opposing forces, direct inhibition of Akt/PKB versus indirect stimulation via secreted insulin. The latter mechanism is dominant, masking the inhibitory effect. Consequently, pharmacological strategies to knock down IP6K activity might not have the same positive output in the β-cell as in other insulin regulated tissues.11Ysciescopu

Mechanisms regulating intestinal barrier integrity and its pathological implications

The gastrointestinal tract is a specialized organ in which dynamic interactions between host cells and the complex environment occur in addition to food digestion. Together with the chemical barrier of the mucosal layer and the cellular immune system, the epithelial cell layer performs a pivotal role as the first physical barrier against external factors and maintains a symbiotic relationship with commensal bacteria. The tight junction proteins, including occludin, claudins, and zonula occludens, are crucial for the maintenance of epithelial barrier integrity. To allow the transport of essential molecules and restrict harmful substances, the intracellular signaling transduction system and a number of extracellular stimuli such as cytokines, small GTPases, and post-translational modifications dynamically modulate the tight junction protein complexes. An imbalance in these regulations leads to compromised barrier integrity and is linked with pathological conditions. Despite the obscurity of the causal relationship, the loss of barrier integrity is considered to contribute to inflammatory bowel disease, obesity, and metabolic disorders. The elucidation of the role of diseases in barrier integrity and the underlying regulatory mechanisms have improved our understanding of the intestinal barrier to allow the development of novel and potent therapeutic approaches.11Ysciescopuskc

REACTION CHARACTERISTICS OF TWO WATER GAS SHIFT CATALYSTS IN A BUBBLING FLUIDIZED BED REACTOR FOR SEWGS PROCESS

Reaction characteristics of two WGS catalysts for SEWGS process were investigated in a bubbling fluidized bed reactor. The commercial low temperature WGS catalyst produced by Süd-chemie and new catalyst produced by spray-drying method were used as bed materials. Reaction temperature, steam/CO ratio, and gas velocity were considered as experimental variables. Moreover, long-term operation results of two WGS catalysts were compared as well

The Interaction of Phospholipase C-{beta}3 with Shank2 Regulates mGluR-mediated Calcium Signal

Phospholipase C-{beta} isozymes that are activated by G protein-coupled receptors (GPCR) and heterotrimeric G proteins carry a PSD-95/Dlg/ZO-1 (PDZ) domain binding motif at their C terminus. Through interactions with PDZ domains, this motif may endow the PLC-{beta} isozyme with specific roles in GPCR signaling events that occur in compartmentalized regions of the plasma membrane. In this study, we identified the interaction of PLC-{beta}3 with Shank2, a PDZ domain-containing multimodular scaffold in the postsynaptic density (PSD). The C terminus of PLC-{beta}3, but not other PLC-{beta} isotypes, specifically interacts with the PDZ domain of Shank2. Homer 1b, a Shank-interacting protein that is linked to group I metabotropic glutamate receptors and IP3 receptors, forms a multiple complex with Shank2 and PLC-{beta}3. Importantly, microinjection of a synthetic peptide specifically mimicking the C terminus of PLC-{beta}3 markedly reduces the mGluR-mediated intracellular calcium response. These results demonstrate that Shank2 brings PLC-{beta}3 closer to Homer 1b and constitutes an efficient mGluR-coupled signaling pathway in the PSD region of neuronal synapses

Plasma cell granuloma in cyclosporine-induced gingival overgrowth: a report of two cases with immunohistochemical positivity of interleukin-6 and phospholipase C-gamma1.

We report two cases of gingival plasma cell granuloma in a 34-yr-old and 40-yr-old two male renal transplant recipients with cyclosporine A (CsA)-induced gingival overgrowth (GO). Histologically, these lesions were composed of mature plasma cells, showing polyclonality for both lambda and kappa light chains and fibrovascular connective tissue stroma. In addition to the fact that CsA-induced plasma cell granuloma is rare, the salient features of our cases were the secretion of interleukin-6 and overexpression of phospholipase C- gamma 1 of the tumor cells, which may explain the mechanisms of CsA- induced GO

Plasmonic Terahertz Wave Detector Based on Silicon Field-Effect Transistors with Asymmetric Source and Drain Structures

In this paper, we present the validity and potential capacity of a modeling and simulation environment for the nonresonant plasmonic terahertz (THz) detector based on the silicon (Si) field-effect transistor (FET) with a technology computer-aided design (TCAD) platform. The nonresonant and "overdamped" plasma-wave behaviors have been modeled by introducing a quasi-plasma electron charge box as a two-dimensional electron gas (2DEG) in the channel region only around the source side of Si FETs. Based on the coupled nonresonant plasma-wave physics and continuity equation on the TCAD platform, the alternate-current (AC) signal as an incoming THz wave radiation successfully induced a direct-current (DC) drain-to-source output voltage as a detection signal in a sub-THz frequency regime under the asymmetric boundary conditions with a external capacitance between the gate and drain. The average propagation length and density of a quasi-plasma have been confirmed as around 100 nm and 1x10(19)/cm(3), respectively, through the transient simulation of Si FETs with the modulated 2DEG at 0.7 THz. We investigated the incoming radiation frequency dependencies on the characteristics of the plasmonic THz detector operating in sub-THz nonresonant regime by using the quasi-plasma modeling on TCAD platform. The simulated dependences of the photoresponse with quasi-plasma 2DEG modeling on the structural parameters such as gate length and dielectric thickness confirmed the operation principle of the nonresonant plasmonic THz detector in the Si PET structure. The proposed methodologies provide the physical design platform for developing novel plasmonic THz detectors operating in the nonresonant detection mode.open3

THE EFFECT OF SHOULDER MOBILITY ON AGONIST AND SYNERGIST DURING SHOULDER PRESS

The purpose of this study was to investigate the effect of shoulder mobility score on agonist and synergist muscle activation during shoulder press and to provide an underpinning fundamental to optimize the training effect while reducing the risk of injuries when instructing training in the field. The participants were divided to two different groups according to individual shoulder mobility score which is part of the Functional Movement Screen (FMS). There were five participants in the score of 3 group (upper group) and six included in the group with the score of less than 3 (lower group). The results of this study revealed that the shoulder mobility score showed a negative correlation with the ratio of the left and right latissimus dorsi/anterior deltoid muscle activation in the concentric contraction phase (

Insulin modulates the frequency of Ca2+ oscillations in mouse pancreatic islets

Pancreatic islets can adapt to oscillatory glucose to produce synchronous insulin pulses. Can islets adapt to other oscillatory stimuli, specifically insulin? To answer this question, we stimulated islets with pulses of exogenous insulin and measured their Ca2+ oscillations. We observed that sufficiently high insulin (>500 nM) with an optimal pulse period (similar to 4 min) could make islets to produce synchronous Ca2+ oscillations. Glucose and insulin, which are key stimulatory factors of islets, modulate islet Ca2+ oscillations differently. Glucose increases the active-to-silent ratio of phases, whereas insulin increases the period of the oscillation. To examine the dual modulation, we adopted a phase oscillator model that incorporated the phase and frequency modulations. This mathematical model showed that out-of-phase oscillations of glucose and insulin were more effective at synchronizing islet Ca2+ oscillations than in-phase stimuli. This finding suggests that a phase shift in glucose and insulin oscillations can enhance inter-islet synchronization.111Ysciescopu