A 3000 year chronology of North Anatolian Fault ruptures, utilizing magnetic susceptibility trench logging, near Lake Ladik, Turkey

Understanding the irregularity of seismic cycles: A case study in Turke

Development of paleoseismic trench logging and dating techniques: a case study on the Central North Anatolian Fault

The North Anatolian Fault (NAF) is a dextral strike slip fault zone extending ~1400km in an arc across northern Turkey. This study seeks to further constrain the timing of ground rupturing earthquakes of the NAF while developing the techniques used in paleoseismology. A paleoseismic trench was opened ~2.7km NW of Destek on a segment which ruptured (for ~280km) in the 1943 Tosya Earthquake (Mw:7.7). The trench site comprises a pop-up structure formed by a small releasing step-over at a restraining bend which has caused progressive growth of an upslope facing scarp. The trench is situated across the main fault trace and a trapped sedimentary sequence that includes several paleosoils. The stratigraphy is expected to be Late Holocene and historic in age due to the high level of activity on the NAF, although this has yet to be confirmed by radiometric dating. Preliminary interpretation of the trench stratigraphy indicates a record of up to 6 paleoearthquake events, the presence of an angular unconformity suggests the record may be incomplete beyond the 3 most recent events on this strand.Subtle contrasts in stratigraphy made conventional face logging difficult and was therefore augmented by mapping the magnetic susceptibility (MS) of the west wall. Approximately 6000 measurements were made using a Bartington MS2 Magnetic Susceptibility Meter with a MS2E (point) Sensor with a 5cm vertical spacing and a 20cm horizontal spacing predominantly on one side of the trench. A pilot test led to development of a strategy of moving the sensor to the nearest exposure of coarse sand or finer grained material where possible to minimize the noise generated by individual clasts. To negate the sensitivity of the MS logging method to variations in temperature the survey was conducted at night. Plotted data clearly shows the contact between rock units, the rock-soil interface (reflecting fault juxtaposition), anthropogenic influence and some soil stratigraphy. Other paleoseismic investigations on this section of the NAF (Hartleb R. et al 2003 and Yoshioka T. et al 2000) have encountered out-of-stratigraphic-order ranges in 14C ages. They attributed this to reworking, in addition to which the effects of long term human occupation are likely to be similar. The trench yielded a large amount of datable material including 158 charcoal and 140 minute gastropod samples, and some ceramic, bone and slag samples. Unlike charcoal and bone fragments, fragile minute gastropods are unlikely to have been transported, reworked or used by humans, ultimately providing improved accuracy of temporal constraints on paleoearthquakes. Using both charcoal and gastropod samples, the trench chronology can be established and the use of minute gastropods for dating paleoearthquakes can be critiqued

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

A Simplified In Situ

From the 20th International Radiocarbon Conference held in Kona, Hawaii, USA, May 31-June 3, 2009.We describe the design, construction, and testing of a new, simplified in situ radiocarbon extraction system at the University of Arizona. Blank levels for the new system are low ((234 +- 11) x 10^3 atoms (1 sigma; n = 7)) and stable. The precision of a given measurement depends on the concentration of 14C, but is typically <5% for concentrations of 100 x 10^3 atoms g^(-1) or more. The new system is relatively small and easy to construct, costs significantly less than the original in situ 14C extraction system at Arizona, and lends itself to future automation.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Independent age estimates resolve the controversy of ancient human footprints at White Sands

Human footprints at White Sands National Park, New Mexico, USA, reportedly date to between ~23,000 and 21,000 years ago according to radiocarbon dating of seeds from the aquatic plant Ruppia cirrhosa. These ages remain controversial because of potential old carbon reservoir effects that could compromise their accuracy. We present new calibrated 14C ages of terrestrial pollen collected from the same stratigraphic horizons as those of the Ruppia seeds, along with optically stimulated luminescence ages of sediments from within the human footprint–bearing sequence, to evaluate the veracity of the seed ages. The results show that the chronologic framework originally established for the White Sands footprints is robust and reaffirm that humans were present in North America during the Last Glacial Maximum

Evaluation and diagnostic potential of circulating extracellular vesicle-associated microRNAs in adrenocortical tumors

There is no available blood marker for the preoperative diagnosis of adrenocortical malignancy. The objective of this study was to investigate the expression of extracellular vesicle-associated microRNAs and their diagnostic potential in plasma samples of patients suffering from adrenocortical tumors. Extracellular vesicles were isolated either by using Total Exosome Isolation Kit or by differential centrifugation/ultracentrifugation. Preoperative plasma extracellular vesicle samples of 6 adrenocortical adenomas (ACA) and 6 histologically verified adrenocortical cancer (ACC) were first screened by Taqman Human Microarray A-cards. Based on the results of screening, two miRNAs were selected and validated by targeted quantitative real-time PCR. The validation cohort included 18 ACAs and 16 ACCs. Beside RNA analysis, extracellular vesicle preparations were also assessed by transmission electron microscopy, flow cytometry and dynamic light scattering. Significant overexpression of hsa-miR-101 and hsa-miR-483-5p in ACC relative to ACA samples has been validated. Receiver operator characteristics of data revealed dCT hsa-miR-483-5p normalized to cel-miR-39 to have the highest diagnostic accuracy (area under curve 0.965), the sensitivity and the specifity were 87.5 and 94.44, respectively. Extracellular vesicle-associated hsa-miR-483-5p thus appears to be a promising minimally invasive biomarker in the preoperative diagnosis of ACC but needs further validation in larger cohorts of patients

Identification of Serum MicroRNAs as Novel Non-Invasive Biomarkers for Early Detection of Gastric Cancer

BACKGROUND: To investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China. METHODOLOGY/PRINCIPAL FINDINGS: All subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy. CONCLUSIONS/SIGNIFICANCE: These data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC

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