The tegula tango: A coevolutionary dance of interacting, positively selected sperm and egg proteins

Reproductive proteins commonly show signs of rapid divergence driven by positive selection. The mechanisms driving these changes have remained ambiguous in part because interacting male and female proteins have rarely been examined. We isolate an egg protein the vitelline envelope receptor for lysin (VERL) from Tegula, a genus of free-spawning marine snails. Like VERL from abalone, Tegula VERL is a major component of the VE surrounding the egg, includes a conserved zona pellucida (ZP) domain at its C-terminus, and possesses a unique, negatively charged domain of about 150 amino acids implicated in interactions with the positively charged lysin. Unlike for abalone VERL, where this unique VERL domain occurs in a tandem array of 22 repeats, Tegula VERL has just one such domain. Interspecific comparisons show that both lysin and the VERL domain diverge via positive selection, whereas the ZP domain evolves neutrally. Rates of nonsynonymous substitution are correlated between lysin and the VERL domain, consistent with sexual antagonism, although lineage-specific effects, perhaps owing to different ecologies, may alter the relative evolutionary rates of sperm- and egg-borne proteins. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution

Molecular aging and rejuvenation of human muscle stem cells

Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth factor beta (TGF-β)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular understanding, combined with data that human satellite cells remain intrinsically young, introduced novel therapeutic targets. Indeed, activation of MAPK/Notch restored ‘youthful’ myogenic responses to satellite cells from 70-year-old humans, rendering them similar to cells from 20-year-old humans. These findings strongly suggest that aging of human muscle maintenance and repair can be reversed by ‘youthful’ calibration of specific molecular pathways

Trajectory shifts in the Arctic and Subarctic freshwater cycle

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of American Association for the Advancement of Science for personal use, not for redistribution. The definitive version was published in Science 313 (2006): 1061-1066, doi:10.1126/science.1122593.Manifold changes in the freshwater cycle of high-latitude lands and oceans have been reported in the past few years. A synthesis of these changes in sources of freshwater and in ocean freshwater storage illustrates the complementary and synoptic temporal pattern and magnitude of these changes over the past 50 years. Increasing river discharge anomalies and excess net precipitation on the ocean contributed ~20,000 km3 of fresh water to the Arctic and high latitude North Atlantic oceans from lows in the 1960s to highs in the 1990s. Sea ice attrition provided another ~15,000 km3, and glacial melt added ~2000 km3. The sum of anomalous inputs from these freshwater sources matched the amount and rate at which fresh water accumulated in the North Atlantic during much of the period from 1965 through 1995. The changes in freshwater inputs and ocean storage occurred in conjunction with the amplifying North Atlantic Oscillation and rising air temperatures. Fresh water may now be accumulating in the Arctic Ocean and will likely be exported southward if and when the North Atlantic Oscillation enters into a new high phase.Funding was provided by NSF (grants OPP-0229302, OPP- 0436118, OPP-0327664, OPP-0352754, OPP-0519840, OCE- 0326778), ONR (grant N00014-02-1-0305) and NASA (grant IDS-03-0000-0145)

Changes in Greenland’s peripheral glaciers linked to the North Atlantic Oscillation

Glaciers and ice caps peripheral to the main Greenland Ice Sheet contribute markedly to sea-level rise1,2,3. Their changes and variability, however, have been difficult to quantify on multi-decadal timescales due to an absence of long-term data4. Here, using historical aerial surveys, expedition photographs, spy satellite imagery and new remote-sensing products, we map glacier length fluctuations of approximately 350 peripheral glaciers and ice caps in East and West Greenland since 1890. Peripheral glaciers are found to have recently undergone a widespread and significant retreat at rates of 12.2 m per year and 16.6 m per year in East and West Greenland, respectively; these changes are exceeded in severity only by the early twentieth century post-Little-Ice-Age retreat. Regional changes in ice volume, as reflected by glacier length, are further shown to be related to changes in precipitation associated with the North Atlantic Oscillation (NAO), with a distinct east–west asymmetry; positive phases of the NAO increase accumulation, and thereby glacier growth, in the eastern periphery, whereas opposite effects are observed in the western periphery. Thus, with projected trends towards positive NAO in the future5,6, eastern peripheral glaciers may remain relatively stable, while western peripheral glaciers will continue to diminish

Interleukin-2 therapy in patients with HIV infection

BACKGROUND Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. RESULTS In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. CONCLUSIONS Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].

Ocean circulation and Tropical Variability in the Coupled Model ECHAM5/MPI-OM

This paper describes the mean ocean circulation and the tropical variability simulated by the Max Planck Institute for Meteorology (MPI-M) coupled atmosphere–ocean general circulation model (AOGCM). Results are presented from a version of the coupled model that served as a prototype for the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) simulations. The model does not require flux adjustment to maintain a stable climate. A control simulation with present-day greenhouse gases is analyzed, and the simulation of key oceanic features, such as sea surface temperatures (SSTs), large-scale circulation, meridional heat and freshwater transports, and sea ice are compared with observations. A parameterization that accounts for the effect of ocean currents on surface wind stress is implemented in the model. The largest impact of this parameterization is in the tropical Pacific, where the mean state is significantly improved: the strength of the trade winds and the associated equatorial upwelling weaken, and there is a reduction of the model’s equatorial cold SST bias by more than 1 K. Equatorial SST variability also becomes more realistic. The strength of the variability is reduced by about 30% in the eastern equatorial Pacific and the extension of SST variability into the warm pool is significantly reduced. The dominant El Niño–Southern Oscillation (ENSO) period shifts from 3 to 4 yr. Without the parameterization an unrealistically strong westward propagation of SST anomalies is simulated. The reasons for the changes in variability are linked to changes in both the mean state and to a reduction in atmospheric sensitivity to SST changes and oceanic sensitivity to wind anomalies

The western Arctic boundary current at 152°W : structure, variability, and transport

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 56 (2009): 1164-1181, doi:10.1016/j.dsr2.2008.10.014.From August 2002 to September 2004 a high-resolution mooring array was maintained across the western Arctic boundary current in the Beaufort Sea north of Alaska. The array consisted of profiling instrumentation, providing a timeseries of vertical sections of the current. Here we present the first-year velocity measurements, with emphasis on the Pacific water component of the current. The mean flow is characterized as a bottom-intensified jet of O(15 cm s-1) directed to the east, trapped to the shelfbreak near 100 m depth. Its width scale is only 10-15 km. Seasonally the flow has distinct configurations. During summer it becomes surface-intensified as it advects buoyant Alaskan Coastal Water. In fall and winter the current often reverses (flows westward) under upwelling-favorable winds. Between the storms, as the eastward flow re-establishes, the current develops a deep extension to depths exceeding 700 m. In spring the bottom-trapped flow advects winter-transformed Pacific water emanating from the Chukchi Sea. The year-long mean volume transport of Pacific Water is 0.13±0.08 Sv to the east, which is less than 20% of the long-term mean Bering Strait inflow. This implies that most of the Pacific water entering the Arctic goes elsewhere, contrary to expected dynamics and previous modeling results. Possible reasons for this are discussed. The mean Atlantic water transport (to 800 m depth) is 0.047±0.026 Sv, also smaller than anticipated.AN was funded by the Swedish Research Council; RP, PF, and DT were funded by grant N00014-02-1-0317 of the Office of Naval Research