Objective: HDL in plasma is a heterogeneous group of lipoproteins typically containing apoA-I as the principal protein. Most HDLs contain additional proteins from a palate of nearly 100 HDL-associated polypeptides. We hypothesized that some of these proteins define distinct and stable apoA-I HDL subspecies with unique proteomes that drive function and associations with disease. Approach and Results: We produced 17 plasma pools from 80 normolipidemic human participants (32 male, 48 female; aged 21 to 66 years). Using immunoaffinity isolation techniques, we isolated apoA-I containing species from plasma and then used antibodies to 16 additional HDL protein components to isolate compositional subspecies. We characterized previously described HDL subspecies containing apoA-II, apoC-III and apoE; and 13 novel HDL subspecies defined by presence of apoA-IV, apoC-I, apoC-II, apoJ, alpha-1-antitrypsin, alpha-2-macroglobulin, plasminogen, fibrinogen, ceruloplasmin, haptoglobin, paraoxonase-1, apoL-I, or complement C3. The novel species ranged in abundance from 1–18% of total plasma apoA-I. Their concentrations were stable over time as demonstrated by intra-class correlations in repeated sampling from the same participants over 3–24 months (0.33 – 0.86; mean 0.62). Some proteomes of the subspecies relative to total HDL were strongly correlated, often among subspecies defined by similar functions: lipid metabolism, hemostasis, anti-oxidant, or anti-inflammatory. Permutation analysis showed that the proteomes of 12 of the 16 subspecies differed significantly from that of total HDL. Conclusions: Taken together, correlation and permutation analyses support speciation of HDL. Functional studies of these novel subspecies and determination of their relation to diseases may provide new avenues to understand the HDL system of lipoproteins.

Earthquake hypocenters recorded in the Andean Southern Puna seismic array (25-28°S, 70-65°W) provide new constraints on the shape of the subducting Nazca plate beneath the Puna plateau, the transition into the Chilean-Pampean flat slab and the thermal state of the mantle and crust. Some 270 new mantle hypocenters suggest that the subducting slab under the Puna shoals into the flat-slab segment more abruptly and farther to the north than previously indicated. The revised geometry is consistent with the Central Volcanic Zone Incapillo caldera being the southernmost center with Pleistocene activity until reaching the southern side of the flat-slab region. Evidence for the revised slab geometry includes three well-defined hypocenter clusters in the Pipanaco nest (27.5-29°S, 68-66°W), which are interpreted to reflect slab-bending stresses. A few low-magnitude earthquakes with strongly attenuated S waves in the long-recognized Antofalla teleseismic gap (25.5-27.5°S) support a continuous slab under the Southern Puna. The paucity of gap earthquakes and the presence of mafic magmas are consistent with a hot mantle wedge reflecting recent lithospheric delamination. Evidence for a hot overlaying Puna crust comes from new crustal earthquake hypocenters concentrated at depths shallower than 5 km. Two notable short-duration swarms were recorded under the resurgent dome of the~2 Ma back-arc Cerro Galán caldera and the near-arc Cerro Torta dome. New crustal earthquake focal mechanisms from 17 events in the array along with two existing mechanisms have strike slip, oblique reverse, and oblique normal solutions fitting with regional E-W compression and N-S extension.

[1] The high elevation of the southern Puna plateau, the widespread melting of its crust, the gap in intermediate depth seismicity and the recent eruptions of ignimbrite complexes can be explained by delamination of the lithospheric mantle beneath it. To test this hypothesis, an array consisting of 73 broad band and short period seismic stations was deployed in the region for a period of 2 years starting in 2007. We inverted the data using the two plane wave approach and obtained 1-D and 3-D Rayleigh wave phase velocities. Our dispersion curve shows that at short periods (<70 s) the phase velocities are slightly higher than those of the Tibetan plateau and lower than those of the Anatolian plateau. At periods of 100-140 s we observe a low velocity zone that might be remnant hot asthenosphere below a flat slab (7-10 Ma). We estimate the average continental lithosphere thickness for the region to be between 100 and 130 km. Our three-dimensional Rayleigh wave phase velocities show a high velocity anomaly at low frequencies (0.007, 0.008, and 0.009 Hz) slightly to the north of Cerro Galan. This would be consistent with the hypothesis of delamination in which a piece of lithosphere has detached and caused upwelling of hot asthenosphere, which in turn caused widespread alkaline-collision related volcanism. This interpretation is also corroborated by our shear wave velocity model, where a high velocity anomaly beneath the northern edge of Cerro Galan at 130 km depth is interpreted as the delaminated block on top of the subducting Nazca slab.