Targeting of nucleo‑cytoplasmic transport factor exportin 1 in malignancy

The US Navy is currently considering the introduction of a Flight III variant beginning with DDG-123 in Fiscal Year 2016. The new design incorporates a new combat system and associated power and cooling upgrades. The overall system improvements increase the payload of the ship and the resulting increased displacement has a negative impact on the service life allowance for range, fuel consumption and sea-keeping characteristics. The present objective is to increase the hull displacement without resistance and sea-keeping penalty and with minimal modifications to the baseline DTMB-5415 design (open literature surrogate of the existing DDG-51 hull form) by using retrofitted blisters in the form of side hull expansions and a bow-bulb. The investigation makes use of high-performance CFD computing for analysis of wave cancellation mechanisms. A candidate modified 5415 design with both blisters and bow bulb shows a resistance reduction of ~11% w.r.t.the baseline 5415 in the design speed range of 15-19 knots, even though the displacement is increased by 8%, such that the transport factor is increased by 19%.

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Regulation of Na+ pump expression by vascular smooth muscle cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.4.h1869 ◽

2001 ◽

Vol 280 (4) ◽

pp. H1869-H1874 ◽

Cited By ~ 8

Author(s):

Aslihan Aydemir-Koksoy ◽

Julius C. Allen

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Mammalian Cells ◽

Muscle Cells ◽

Transport Processes ◽

Western Blots ◽

Cytoplasmic Transport ◽

Low K

The Na+ pump and its regulation is important for maintaining membrane potential and transmembrane Na+gradient in all mammalian cells and thus is essential for cell survival and function. Vascular smooth muscle cells (VSMC) have a relatively low number of pump sites on their membrane compared with other cells. We wished to determine the mechanisms for regulating the number of pump sites in these cells. We used canine saphenous vein VSMC cultured in 10% serum and passaged one time. These cells were subcultured in 5% serum media with low K+ (1 mM vs. control of 5 mM), and their pump expression was assessed. These VSMC upregulated their pump sites as early as 4 h after treatment (measured by [3H]ouabain binding). At this early time point, there was no detectable increase in protein expression of either α1- or β1-subunits of the pump shown by Western blots. When the cells were treated with the phosphoinositide 3-kinase (PI-3-K) inhibitor LY-294002 (which is known to inhibit cytoplasmic transport processes) in low-K+ media, the pump site upregulation was inhibited. These data suggest that the low-K+-induced upregulation of Na+ pump number can occur by translocation of preformed pumps from intracellular stores.

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