A Network of SLC and ABC Transporter and DME Genes Involved in Remote Sensing and Signaling in the Gut-Liver-Kidney Axis.

Genes central to drug absorption, distribution, metabolism and elimination (ADME) also regulate numerous endogenous molecules. The Remote Sensing and Signaling Hypothesis argues that an ADME gene-centered network-including SLC and ABC "drug" transporters, "drug" metabolizing enzymes (DMEs), and regulatory genes-is essential for inter-organ communication via metabolites, signaling molecules, antioxidants, gut microbiome products, uremic solutes, and uremic toxins. By cross-tissue co-expression network analysis, the gut, liver, and kidney (GLK) formed highly connected tissue-specific clusters of SLC transporters, ABC transporters, and DMEs. SLC22, SLC25 and SLC35 families were network hubs, having more inter-organ and intra-organ connections than other families. Analysis of the GLK network revealed key physiological pathways (e.g., involving bile acids and uric acid). A search for additional genes interacting with the network identified HNF4α, HNF1α, and PXR. Knockout gene expression data confirmed ~60-70% of predictions of ADME gene regulation by these transcription factors. Using the GLK network and known ADME genes, we built a tentative gut-liver-kidney "remote sensing and signaling network" consisting of SLC and ABC transporters, as well as DMEs and regulatory proteins. Together with protein-protein interactions to prioritize likely functional connections, this network suggests how multi-specificity combines with oligo-specificity and mono-specificity to regulate homeostasis of numerous endogenous small molecules

Characteristics of Magnetohydrodynamic Oscillations Observed with Michelson Doppler Imager

We report on the spatial distribution of magnetogram oscillatory power and phase angles between velocity and magnetogram signals as observed with the Michelson Doppler Imager. The dataset is 151.25 arcsec times 151.25 arcsec containing sunspot from Dec 2, 1997 with a temporal sampling interval of 60 seconds and spatial sampling of 0.605 arcsec. Simultaneously observed continuum intensity and surface velocity accompany the magnetic information. We focus on three frequency regimes: 0.5-1.0, 3.0-3.5 and 5.5-6.0 mHz corresponding roughly to timescales of magnetic evolution, p-modes and the 3 minute resonant sunspot oscillation. Significant low frequency magnetogram power is found in lower flux pixels, 100-300 Gauss, in a striking ring with filamentary structure surrounding sunspot. Five minute magnetogram power peaks in extended regions of flux 600-800 Gauss. The 3 minute oscillation is observed in sunspot umbra in pixels whose flux measures 1300-1500 Gauss. Phase angles of approximately -90 degrees between velocity and magnetic flux in the 3.0-3.5 and 5.5-6.0 mHz regimes are found in regions of significant cross amplitude.Comment: 4 Pages, 4 Figures -- For better Figure files see: http://www.astro.ucla.edu/~norton/pub_list.htm

Generation of an expandable intermediate mesoderm restricted progenitor cell line from human pluripotent stem cells.

The field of tissue engineering entered a new era with the development of human pluripotent stem cells (hPSCs), which are capable of unlimited expansion whilst retaining the potential to differentiate into all mature cell populations. However, these cells harbor significant risks, including tumor formation upon transplantation. One way to mitigate this risk is to develop expandable progenitor cell populations with restricted differentiation potential. Here, we used a cellular microarray technology to identify a defined and optimized culture condition that supports the derivation and propagation of a cell population with mesodermal properties. This cell population, referred to as intermediate mesodermal progenitor (IMP) cells, is capable of unlimited expansion, lacks tumor formation potential, and, upon appropriate stimulation, readily acquires properties of a sub-population of kidney cells. Interestingly, IMP cells fail to differentiate into other mesodermally-derived tissues, including blood and heart, suggesting that these cells are restricted to an intermediate mesodermal fate

Chaotic and pseudochaotic attractors of perturbed fractional oscillator

We consider a nonlinear oscillator with fractional derivative of the order alpha. Perturbed by a periodic force, the system exhibits chaotic motion called fractional chaotic attractor (FCA). The FCA is compared to the ``regular'' chaotic attractor. The properties of the FCA are discussed and the ``pseudochaotic'' case is demonstrated.Comment: 20 pages, 7 figure

Factors Associated with Recurrence of Varicose Veins after Thermal Ablation: Results of The Recurrent Veins after Thermal Ablation Study

Background. The goal of this retrospective cohort study (REVATA) was to determine the site, source, and contributory factors of varicose vein recurrence after radiofrequency (RF) and laser ablation. Methods. Seven centers enrolled patients into the study over a 1-year period. All patients underwent previous thermal ablation of the great saphenous vein (GSV), small saphenous vein (SSV), or anterior accessory great saphenous vein (AAGSV). From a specific designed study tool, the etiology of recurrence was identified. Results. 2,380 patients were evaluated during this time frame. A total of 164 patients had varicose vein recurrence at a median of 3 years. GSV ablation was the initial treatment in 159 patients (RF: 33, laser: 126, 52 of these patients had either SSV or AAGSV ablation concurrently). Total or partial GSV recanalization occurred in 47 patients. New AAGSV reflux occurred in 40 patients, and new SSV reflux occurred in 24 patients. Perforator pathology was present in 64% of patients. Conclusion. Recurrence of varicose veins occurred at a median of 3 years after procedure. The four most important factors associated with recurrent veins included perforating veins, recanalized GSV, new AAGSV reflux, and new SSV reflux in decreasing frequency. Patients who underwent RF treatment had a statistically higher rate of recanalization than those treated with laser

Organic Anion and Cation Transporter Expression and Function During Embryonic Kidney Development and in Organ Culture Model Systems

Background Organic anion and cation transporters (OATs, OCTs and OCTNs) mediate the proximal tubular secretion of numerous clinically important compounds, including various commonly prescribed pharmaceuticals. Here, we examine the ontogeny of these transporters in rat embryonic kidney in detail, both in vivo and in two in vitro organ culture models of kidney development, whole embryonic kidney (WEK) culture and culture of induced metanephric mesenchyme (MM). Methods We used QPCR to determine expression levels of transporter genes in rat embryonic kidneys on each day of gestation from ed13 to ed18, in induced and un-induced MM, and on each day of one week of WEK culture. We also used uptake of fluorescein as a novel functional assay of organic anion transporter expression in WEK and MM. Results The developmental induction of the various organic anion and cation transporter genes does not occur uniformly: some genes are induced early (e.g., Oat1 and Oat3, potential early markers of proximal tubulogenesis), and others not till kidney development is relatively advanced (e.g., Oct1, a potential marker of terminal differentiation). We also find that the ontogeny of transporter genes in WEK and MM is similar to that observed in vivo, indicating that these organ culture systems may appropriately model the expression of OATs, OCTs and OCTNs. Conclusion We show that WEK and MM cultures may represent convenient in vitro models for study of the developmental induction of organic anion and cation transporters. Functional organic anion transport as measured by fluorescein uptake was evident by accumulation of the fluorescence in the developing tubule in these organ cultures. By demonstrating the mediated uptake of fluorescein in WEK and MM, we have established a novel in vitro functional assay of transporter function. We find that OATs, OCTs, and OCTNs are differentially expressed during proximal tubule development. Our findings on the renal ontogeny of organic anion and cation transporters could carry implications both for the development of more rational therapeutics for premature infants, as well as for our understanding of proximal tubule differentiation

Magnetic phase diagram of the frustrated S=1/2 chain magnet LiCu_2O_2

We present the results of the magnetization and dielectric constant measurements on untwinned single crystal samples of the frustrated S=1/2 chain cuprate LiCu_2O_2. Novel magnetic phase transitions were observed. A spin flop transition of the spiral spin plane was observed for the field orientations H||a,b. The second magnetic transition was observed at H~15 T for all three principal field directions. This high field magnetic phase is discussed as a collinear spin-modulated phase which is expected for an S=1/2 nearest-neighbor ferromagnetic and next-nearest-neighbor antiferromagnetic chain system