A perceived recent increase in global jellyfish abundance has been portrayed as a symptom of degraded oceans. This perception is based primarily on a few case studies and anecdotal evidence, but a formal analysis of global temporal trends in jellyfish populations has been missing. Here, we analyze all available long-term datasets on changes in jellyfish abundance across multiple coastal stations, using linear and logistic mixed models and effect-size analysis to show that there is no robust evidence for a global increase in jellyfish. Although there has been a small linear increase in jellyfish since the 1970s, this trend was unsubstantiated by effect-size analysis that showed no difference in the proportion of increasing vs. decreasing jellyfish populations over all time periods examined. Rather, the strongest nonrandom trend indicated jellyfish populations undergo larger, worldwide oscillations with an approximate 20-y periodicity, including a rising phase during the 1990s that contributed to the perception of a global increase in jellyfish abundance. Sustained monitoring is required over the next decade to elucidate with statistical confidence whether the weak increasing linear trend in jellyfish after 1970 is an actual shift in the baseline or part of an oscillation. Irrespective of the nature of increase, given the potential damage posed by jellyfish blooms to fisheries, tourism, and other human industries, our findings foretell recurrent phases of rise and fall in jellyfish populations that society should be prepared to face.

Tenofovir (TFV) undergoes renal elimination by a combination of glomerular filtration and active tubular secretion. While transporter-mediated uptake of TFV from the blood into proximal-tubule cells has been well characterized, comparatively little is known about the efflux system responsible for transporting TFV into the lumen during active tubular secretion. Therefore, members of the ATP-binding cassette family of efflux pumps expressed at the apical side of proximal-tubule cells were studied for the ability to transport TFV. Studies in multiple independent in vitro systems show TFV not to be a substrate for P glycoprotein (Pgp) or multidrug resistance protein type 2 (MRP2). In contrast to Pgp and MRP2, TFV was observed to be a substrate for MRP4. TFV accumulated to fivefold lower levels in MRP4-overexpressing cells, and its accumulation could be increased by an MRP inhibitor. Furthermore, MRP4-overexpressing cells were found to be 2.0-to 2.5-fold less susceptible to cytotoxicity caused by TFV. ATP-dependent uptake of TFV was observed in membrane vesicles containing MRP4 but not in vesicles lacking the transporter. On the basis of these and previous results, the molecular transport pathway for the active tubular secretion of TFV through renal proximal-tubule cells involves uptake from the blood mediated by human organic anion transporters 1 and 3 and efflux into urine by MRP4. A detailed understanding of the molecular mechanism of TFV active tubular secretion will facilitate the assessment of potential renal drug-drug interactions with coadministered agents.

miCHael n daWson, maRy betH deCKeR, Claudia e. mills, JennifeR e. PuRCell, alenKa maleJ, HeRmes mianzan, sHin-iCHi uye, stefan GelCiCH, and lauRenCe P. madin During the past several decades, high numbers of gelatinous zooplankton species have been reported in many estuarine and coastal ecosystems. Coupled with media-driven public perception, a paradigm has evolved in which the global ocean ecosystems are thought to be heading toward being dominated by "nuisance" jellyfish. We question this current paradigm by presenting a broad overview of gelatinous zooplankton in a historical context to develop the hypothesis that population changes reflect the human-mediated alteration of global ocean ecosystems. To this end, we synthesize information related to the evolutionary context of contemporary gelatinous zooplankton blooms, the human frame of reference for changes in gelatinous zooplankton populations, and whether sufficient data are available to have established the paradigm. We conclude that the current paradigm in which it is believed that there has been a global increase in gelatinous zooplankton is unsubstantiated, and we develop a strategy for addressing the critical questions about long-term, human-related changes in the sea as they relate to gelatinous zooplankton blooms.

jellyfish (Cnidaria, Scyphozoa) blooms appear to be increasing in both intensity and frequency in many coastal areas worldwide, due to multiple hypothesized anthropogenic stressors. Here, we propose that the proliferation of artificial structures-associated with (1) the exponential growth in shipping, aquaculture, and other coastal industries, and (2) coastal protection (collectively, "ocean sprawl")-provides habitat for jellyfish polyps and may be an important driver of the global increase in jellyfish blooms. However, the habitat of the benthic polyps that commonly result in coastal jellyfish blooms has remained elusive, limiting our understanding of the drivers of these blooms. Support for the hypothesized role of ocean sprawl in promoting jellyfish blooms is provided by observations and experimental evidence demonstrating that jellyfish larvae settle in large numbers on artificial structures in coastal waters and develop into dense concentrations of jellyfish-producing polyps.

Global temperatures are rising, and are expected to produce a poleward shift in the distribution of many organisms. We quantified changes in fish assemblages within seagrass meadows of the northern Gulf of Mexico (GOM) between the 1970s and 2006-2007, and observed changes consistent with this forecast. During 2006-2007 we sampled seagrass meadows using the same gears and methods previously employed by R. J. Livingston in coastal waters of northwest Florida throughout the 1970s. Comparisons between datasets revealed numerous additions to the fish fauna during 2006-2007 that were completely absent in the 1970s, including: Lutjanus synagris (lane snapper), Epinephelus morio (red grouper), Chaetodon ocellatus (spotfin butterflyfish), Mycteroperca sp (grouper, non gag), Centropristis philadelphica (rock sea bass), Fistularia tabacaria (bluespotted cornetfish), Ocyurus chrysurus (yellowtail snapper), Thalassoma bifasciatum (bluehead wrasse), Abudefduf saxatilis (sergeant major), Acanthuridae spp. (surgeonfishes) and Sparisoma viride (stoplight parrotfish). Several other species showed large increases in abundance during the interval between 1979 and 2006, including Mycteroperca microlepis (gag grouper, up $ 200 Â ), Lutjanus griseus (gray snapper, up $ 105 Â ), and Nicholsina usta (emerald parrotfish, up $ 22 Â ).All of these are tropical or subtropical species that now make up a greater percentage of seagrass-associated fish assemblages in the northern GOM than in the past. Additionally, we observed regional increases in air and sea surface temperatures (43 1C) during the $ 30 years that separate Livingston's samples and ours that correlate with northern shifts in the distribution of warm-water fishes. Documenting these range shifts is a critical first step in investigating the consequences of global warming for endemic marine communities and fishery production in the northern GOM.

Main conclusions: JeDI is a unique global dataset of GZ taxa, which will provide a 83 benchmark against which future observations can be compared and shifting baselines 84 assessed. The presence of GZ throughout the world's oceans and across the complete global 85

Human immunodeficiency virus protease inhibitors (PIs) modestly affect the plasma pharmacokinetics of tenofovir (TFV; ؊15% to ؉37% change in exposure) following coadministration with the oral prodrug TFV disoproxil fumarate (TDF) by a previously undefined mechanism. TDF permeation was found to be reduced by the combined action of ester cleavage and efflux transport in vitro. Saturable TDF efflux observed in Caco-2 cells suggests that at pharmacologically relevant intestinal concentrations, transport has only a limited effect on TDF absorption, thus minimizing the magnitude of potential intestinal drug interactions. Most tested PIs increased apical-to-basolateral TDF permeation and decreased secretory transport in MDCKII cells overexpressing P-glycoprotein (Pgp; MDCKII-MDR1 cells) and Caco-2 cells. PIs were found to cause a multifactorial effect on the barriers to TDF absorption. All PIs showed similar levels of inhibition of esterase-dependent degradation of TDF in an intestinal subcellular fraction, except for amprenavir, which was found to be a weaker inhibitor. All PIs caused a dose-dependent increase in the accumulation of a model Pgp substrate in MDCKII-MDR1 cells. Pgp inhibition constants ranged from 10.3 M (lopinavir) to >100 M (amprenavir, indinavir, and darunavir). Analogous to hepatic cytochrome P450-mediated drug interactions, we propose that the relative differences in perturbations in TFV plasma levels when TDF is coadministered with PIs are based in part on the net effect of inhibition and induction of intestinal Pgp by PIs. Combined with prior studies, these findings indicate that intestinal absorption is the mechanism for changes in TFV plasma levels when TDF is coadministered with PIs.Tenofovir disoproxil fumarate (TDF; Viread, Gilead Sciences, Inc.), a prodrug of the nucleotide reverse transcriptase inhibitor tenofovir (TFV), is used to effectively deliver TFV across the gut wall. Following absorption, TDF rapidly degrades to TFV and TDF is not observed in the systemic circulation. When administered by itself, TFV has poor oral bioavailability (7). TDF is a common once-a-day backbone for use with human immunodeficiency virus (HIV) protease inhibitors (PIs). Clinical trials have shown TDF with emtricitabine in combination with either lopinavir (LPV) or atazanavir (ATV), each boosted with ritonavir (RTV, or "r" when referred to as a boosting agent), to be efficacious and well tolerated (22,30).Polypharmacy in HIV patients creates the potential for drug interactions (8,35). No interaction between PIs and TDF would be anticipated due to the lack of cytochrome P450 involvement in the elimination pathway of TDF or TFV (25). However, modest changes in TFV plasma pharmacokinetic parameters have been reported for TDF coadministered with PIs. As summarized in Table 1, PIs can be categorized into three different groups based on their effects on TFV plasma pharmacokinetics. The first group encompasses PIs that cause modest increases in TFV plasma exposure (area under the concentration-time curve from 0 h t...

Jellyfish form spectacular blooms throughout the world’s oceans. Jellyfish body plans are characterised by high water and low carbon contents which enables them to grow much larger than non-gelatinous animals of equivalent carbon content and to deviate from non-gelatinous pelagic animals when incorporated into allometric relationships. Jellyfish have, however, been argued to conform to allometric relationships when carbon content is used as the metric for comparison. Here we test the hypothesis that differences in allometric relationships for several key functional parameters remain for jellyfish even after their body sizes are scaled to their carbon content. Data on carbon and nitrogen contents, rates of respiration, excretion, growth, longevity and swimming velocity of jellyfish and other pelagic animals were assembled. Allometric relationships between each variable and the equivalent spherical diameters of jellyfish and other pelagic animals were compared before and after sizes of jellyfish were standardised for their carbon content. Before standardisation, the slopes of the allometric relationships for respiration, excretion and growth were the same for jellyfish and other pelagic taxa but the intercepts differed. After standardisation, slopes and intercepts for respiration were similar but excretion rates of jellyfish were 10× slower, and growth rates 2× faster than those of other pelagic animals. Longevity of jellyfish was independent of size. The slope of the allometric relationship of swimming velocity of jellyfish differed from that of other pelagic animals but because they are larger jellyfish operate at Reynolds numbers approximately 10× greater than those of other pelagic animals of comparable carbon content. We conclude that low carbon and high water contents alone do not explain the differences in the intercepts or slopes of the allometric relationships of jellyfish and other pelagic animals and that the evolutionary longevity of jellyfish and their propensity to form blooms is facilitated by their unique body plans.