Origin of last-glacial loess in the western Yukon-Tanana Upland, central Alaska, USA

Loess is widespread over Alaska, and its accumulation has traditionally been associated with glacial periods. Surprisingly, loess deposits securely dated to the last glacial period are rare in Alaska, and paleowind reconstructions for this time period are limited to inferences from dune orientations. We report a rare occurrence of loess deposits dating to the last glacial period, ~19 ka to ~12 ka, in the Yukon-Tanana Upland. Loess in this area is very coarse grained (abundant coarse silt), with decreases in particle size moving south of the Yukon River, implying that the drainage basin of this river was the main source. Geochemical data show, however, that the Tanana River valley to the south is also a likely distal source. The occurrence of last-glacial loess with sources to both the south and north is explained by both regional, synoptic-scale winds from the northeast and opposing katabatic winds that could have developed from expanded glaciers in both the Brooks Range to the north and the Alaska Range to the south. Based on a comparison with recent climate modeling for the last glacial period, seasonality of dust transport may also have played a role in bringing about contributions from both northern and southern sources

Seasonality of precipitation in the southwestern United States during the late Pleistocene inferred from stable isotopes in herbivore tooth enamel

The late Pleistocene was a climatically dynamic period, with abrupt shifts between cool-wet and warmdry conditions. Increased effective precipitation supported large pluvial lakes and long-lived spring ecosystems in valleys and basins throughout the western and southwestern U.S., but the source and seasonality of the increased precipitation are debated. Increases in the proportions of C4/(C4+ C3) grasses in the diets of large grazers have been ascribed both to increases in summer precipitation and lower atmospheric CO2 levels. Here we present stable carbon and oxygen isotope data from tooth enamel of late Pleistocene herbivores recovered from paleowetland deposits at Tule Spring Fossil Beds National Monument in the Las Vegas Valley of southern Nevada, as well as modern herbivores from the surrounding area. We use these data to investigate whether winter or summer precipitation was responsible for driving the relatively wet hydroclimate conditions that prevailed in the region during the late Pleistocene. We also evaluate whether late Pleistocene grass C4/(C4+ C3) was higher than today, and potential drivers of any changes. Tooth enamel δ18O values for Pleistocene Equus, Bison, and Mammuthus are generally low (average 22.0 ± 0.7‰, 2 s.e., VSMOW) compared to modern equids (27.8 ± 1.5‰), and imply lower water δ18O values (-16.1 ± 0.8‰) than modern precipitation (-10.5‰) or in waters present in active springs and wells in the Las Vegas Valley (-12.9‰), an area dominated by winter precipitation. In contrast, tooth enamel of Camelops (a browser) generally yielded higher δ18O values (23.9 ± 1.1‰), possibly suggesting drought tolerance. Mean δ13C values for the Pleistocene grazers (-6.6 ± 0.7‰, 2 s.e., VPDB) are considerably higher than for modern equids (-9.6 ± 0.4‰) and indicate more consumption of C4 grass (17 ± 5%) than today (4 ± 4%). However, calculated C4 grass consumption in the late Pleistocene is strikingly lower than the proportion of C4 grass taxa currently present in the valley (55-60%). δ13C values in Camelops tooth enamel (-7.7 ± 1.0‰) are interpreted as reflecting moderate consumption (14 ± 8%) of Atriplex (saltbush), a C4 shrub that flourishes in regions with hot, dry summers. Lower water δ18O values, lower abundance of C4 grasses, and the inferred presence of Atriplex are all consistent with general circulation models for the late Pleistocene that show enhanced delivery of winter precipitation, sourced from the north Pacific, into the interior western U.S. but do not support alternative models that infer enhanced delivery of summer precipitation, sourced from the tropics. In addition, we hypothesize that dietary competition among the diverse and abundant Pleistocene fauna may have driven the grazers analyzed here to feed preferentially on C4 grasses. Dietary partitioning, especially when combined with decreased pCO2 levels during the late Pleistocene, can explain the relatively high δ13C values observed in late Pleistocene grazers in the Las Vegas Valley and elsewhere in the southwestern U.S. without requiring additional summer precipitation. Pleistocene hydroclimate parameters derived from dietary and floral records may need to be reevaluated in the context of the potential effects of dietary preferences and lower pCO2 levels on the stability of C3 vs. C4 plants

Geologic setting and stratigraphy of the Ziegler Reservoir fossil site, Snowmass Village, Colorado

The geologic setting of the Ziegler Reservoir fossil site is somewhat unusual—the sediments containing the Pleistocene fossils were deposited in a lake on top of a ridge. The lake basin was formed near Snowmass Village, Colorado (USA) when a glacier flowing down Snowmass Creek Valley became thick enough to overtop a low point in the eastern valley wall and entered the head of Brush Creek Valley. When the glacier retreated at about 155–130 ka, near the end of Marine Oxygen Isotope Stage 6, the Brush Creek Valley lobe left behind a moraine that impounded a small alpine lake. The lake was initially ~10m deep and appears to have been highly productive during most of its existence, based on the abundant and exquisitely preserved organic material present in the sediments. Over time, the basin slowly filled with (mostly) eolian sediment such that by ~87 ka it contained a marsh or wetland rather than a true lake. Open-water conditions returned briefly between ~77 and 55 ka before the impoundment was finally breached to the east, establishing ties with the Brush Creek drainage system and creating an alpine meadow that persisted until historic times

Geologic setting and stratigraphy of the Ziegler Reservoir fossil site, Snowmass Village, Colorado

The geologic setting of the Ziegler Reservoir fossil site is somewhat unusual—the sediments containing the Pleistocene fossils were deposited in a lake on top of a ridge. The lake basin was formed near Snowmass Village, Colorado (USA) when a glacier flowing down Snowmass Creek Valley became thick enough to overtop a low point in the eastern valley wall and entered the head of Brush Creek Valley. When the glacier retreated at about 155–130 ka, near the end of Marine Oxygen Isotope Stage 6, the Brush Creek Valley lobe left behind a moraine that impounded a small alpine lake. The lake was initially ~10m deep and appears to have been highly productive during most of its existence, based on the abundant and exquisitely preserved organic material present in the sediments. Over time, the basin slowly filled with (mostly) eolian sediment such that by ~87 ka it contained a marsh or wetland rather than a true lake. Open-water conditions returned briefly between ~77 and 55 ka before the impoundment was finally breached to the east, establishing ties with the Brush Creek drainage system and creating an alpine meadow that persisted until historic times

Haemolysis during Sample Preparation Alters microRNA Content of Plasma

The presence of cell-free microRNAs (miRNAs) has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases. Nevertheless, the quantification of miRNAs from plasma or serum is made difficult due to inefficient isolation and lack of consensus regarding the optimal reference miRNA. The effect of haemolysis on the quantification and normalisation of miRNAs in plasma has not been investigated in great detail. We found that levels of miR-16, a commonly used reference gene, showed little variation when measured in plasma samples from healthy volunteers or patients with malignant mesothelioma or coronary artery disease. Including samples with evidence of haemolysis led to variation in miR-16 levels and consequently decreased its ability to serve as a reference. The levels of miR-16 and miR-451, both present in significant levels in red blood cells, were proportional to the degree of haemolysis. Measurements of the level of these miRNAs in whole blood, plasma, red blood cells and peripheral blood mononuclear cells revealed that the miRNA content of red blood cells represents the major source of variation in miR-16 and miR-451 levels measured in plasma. Adding lysed red blood cells to non-haemolysed plasma allowed a cut-off level of free haemoglobin to be determined, below which miR-16 and miR-451 levels displayed little variation between individuals. In conclusion, increases in plasma miR-16 and miR-451 are caused by haemolysis. In the absence of haemolysis the levels of both miR-16 and miR-451 are sufficiently constant to serve as normalisers

Selective Release of MicroRNA Species from Normal and Malignant Mammary Epithelial Cells

MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications