A persistent and dynamic East Greenland Ice Sheet over the past 7.5 million years

Climate models show that ice-sheet melt will dominate sea-level rise over the coming centuries, but our understanding of ice-sheet variations before the last interglacial 125,000 years ago remains fragmentary. This is because terrestrial deposits of ancient glacial and interglacial periods1,2,3 are overrun and eroded by more recent glacial advances, and are therefore usually rare, isolated and poorly dated4. In contrast, material shed almost continuously from continents is preserved as marine sediment that can be analysed to infer the time-varying state of major ice sheets. Here we show that the East Greenland Ice Sheet existed over the past 7.5 million years, as indicated by beryllium and aluminium isotopes (10Be and 26Al) in quartz sand removed by deep, ongoing glacial erosion on land and deposited offshore in the marine sedimentary record5,6. During the early Pleistocene epoch, ice cover in East Greenland was dynamic; in contrast, East Greenland was mostly ice-covered during the mid-to-late Pleistocene. The isotope record we present is consistent with distinct signatures of changes in ice sheet behaviour coincident with major climate transitions. Although our data are continuous, they are from low-deposition-rate sites and sourced only from East Greenland. Consequently, the signal of extensive deglaciation during short, intense interglacials could be missed or blurred, and we cannot distinguish between a remnant ice sheet in the East Greenland highlands and a diminished continent-wide ice sheet. A clearer constraint on the behaviour of the ice sheet during past and, ultimately, future interglacial warmth could be produced by 10Be and 26Al records from a coring site with a higher deposition rate. Nonetheless, our analysis challenges the possibility of complete and extended deglaciation over the past several million years

Revised chronology for late Pleistocene Mono Lake sediments based on paleointensity correlation to the global reference curve

Lakes are highly sensitive recorders of climate processes, but are extremely difficult to correlate precisely to ice-core and marine records, especially in the absence of reliable radiocarbon dates. Relative paleointensity (RPI) of Earth's magnetic field is an independent method of correlating high-resolution climate records, and can be applied to both marine and terrestrial sediments, as well as (inversely) correlated to the cosmogenic nuclide records preserved in ice cores. Here we present the correlation of an RPI record from Mono Lake, California to GLOPIS, the Global PaleoIntensity Stack, which increases the age estimation of the basal Mono Lake sediments by > 20 000 yr (20 kyr), from ∼40 ka (kyr before present) to 67 ka. The Mono Lake sediments thus preserve paleoclimatic records of most of the last glacial period, from 67 to 14 ka. In addition, the paleointensity-based age of 40 ka for the geomagnetic excursion preserved at Mono Lake indicates that this is a record of the global Laschamp excursion

Afadin orients cell division to position the tubule lumen in developing renal tubules

In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity in vivo is not known. We recently found the F-actin binding protein Afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown. Here we demonstrate Afadin is required for lumen continuity by orienting the mitotic spindle during cell division. Using an in vitro 3D cyst model, we find Afadin localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle. In tubules, cell division may be oriented relative to two axes, longitudinal and apical-basal. Unexpectedly, in vivo examination of early stage developing nephron tubules reveals cell division is not oriented in the longitudinal (or planar polarized) axis. However, cell division is oriented perpendicular to the apical-basal axis. Absence of Afadin in vivo leads to misorientation of apical-basal cell division in nephron tubules. Together these results support a model whereby Afadin determines lumen placement by directing apical-basal spindle orientation, which generates a continuous lumen and normal tubule morphogenesis

Cosmogenic nuclides indicate that boulder fields are dynamic, ancient, multigenerational features

Boulder fields are found throughout the world; yet, the history of these features, as well as the processes that form them, remain poorly understood. In high and mid-latitudes, boulder fields are thought to form and be active during glacial periods; however, few quantitative data support this assertion. Here, we use in situ cosmogenic 10Be and 26Al to quantify the near-surface history of 52 samples in and around the largest boulder field in North America, Hickory Run, in central Pennsylvania, USA. Boulder surface 10Be concentrations (n = 43) increase downslope, indicate minimum near-surface histories of 70-600 k.y., and are not correlated with lithology or boulder size. Measurements of samples from the top and bottom of one boulder and three underlying clasts as well as 26Al/10Be ratios (n = 25) suggest that at least some boulders have complex exposure histories caused by flipping and/or cover by other rocks, soil, or ice. Cosmogenic nuclide data demonstrate that Hickory Run, and likely other boulder fields, are dynamic features that persist through multiple glacial-interglacial cycles because of boulder resistance to weathering and erosion. Long and complex boulder histories suggest that climatic interpretations based on the presence of these rocky landforms are likely over simplifications

Donor Complications Following Laparoscopic Compared to Hand-Assisted Living Donor Nephrectomy: An Analysis of the Literature

There are two approaches to laparoscopic donor nephrectomy: standard laparoscopic donor nephrectomy (LDN) and hand-assisted laparoscopic donor nephrectomy (HALDN). In this study we report the operative statistics and donor complications associated with LDN and HALDN from large-center peer-reviewed publications. Methods. We conducted PubMed and Ovid searches to identify LDN and HALDN outcome studies that were published after 2004. Results. There were 37 peer-reviewed studies, each with more than 150 patients. Cumulatively, over 9000 patients were included in this study. LDN donors experienced a higher rate of intraoperative complications than HALDN donors (5.2% versus. 2.0%, P < .001). Investigators did not report a significant difference in the rate of major postoperative complications between the two groups (LDN 0.5% versus HALDN 0.7%, P = .111). However, conversion to open procedures from vascular injury was reported more frequently in LDN procedures (0.8% versus 0.4%, P = .047). Conclusion. At present there is no evidence to support the use of one laparoscopic approach in preference to the other. There are trends in the data suggesting that intraoperative injuries are more common in LDN while minor postoperative complications are more common in HALDN

SHCal13 Southern Hemisphere calibration, 0–50,000 years cal BP

The Southern Hemisphere SHCal04 radiocarbon calibration curve has been updated with the addition of new data sets extending measurements to 2145 cal BP and including the ANSTO Younger Dryas Huon pine data set. Outside the range of measured data, the curve is based upon the Northern Hemisphere data sets as presented in IntCal13, with an interhemispheric offset averaging 43 ± 23 yr modeled by an autoregressive process to represent the short-term correlations in the offset

A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation

SummaryCalcium/calmodulin (Ca2+/CaM)-dependent protein kinase II (CaMKII) couples increases in cellular Ca2+ to fundamental responses in excitable cells. CaMKII was identified over 20 years ago by activation dependence on Ca2+/CaM, but recent evidence shows that CaMKII activity is also enhanced by pro-oxidant conditions. Here we show that oxidation of paired regulatory domain methionine residues sustains CaMKII activity in the absence of Ca2+/CaM. CaMKII is activated by angiotensin II (AngII)-induced oxidation, leading to apoptosis in cardiomyocytes both in vitro and in vivo. CaMKII oxidation is reversed by methionine sulfoxide reductase A (MsrA), and MsrA−/− mice show exaggerated CaMKII oxidation and myocardial apoptosis, impaired cardiac function, and increased mortality after myocardial infarction. Our data demonstrate a dynamic mechanism for CaMKII activation by oxidation and highlight the critical importance of oxidation-dependent CaMKII activation to AngII and ischemic myocardial apoptosis

HTLV-1 propels thymic human T cell development in “human immune system” Rag2-/- IL-2R γc-/- Mice

Alteration of early haematopoietic development is thought to be responsible for the onset of immature leukemias and lymphomas. We have previously demonstrated that TaxHTLV-1 interferes with ß-selection, an important checkpoint of early thymopoiesis, indicating that human T-cell leukemia virus type 1 (HTLV-1) infection has the potential to perturb thymic human αβ T-cell development. To verify that inference and to clarify the impact of HTLV-1 infection on human T-cell development, we investigated the in vivo effects of HTLV-1 infection in a “Human Immune System” (HIS) Rag2-/-γc-/- mouse model. These mice were infected with HTLV-1, at a time when the three main subpopulations of human thymocytes have been detected. In all but two inoculated mice, the HTLV-1 provirus was found integrated in thymocytes; the proviral load increased with the length of the infection period. In the HTLV-1-infected mice we observed alterations in human T-cell development, the extent of which correlated with the proviral load. Thus, in the thymus of HTLV-1-infected HIS Rag2-/-γc-/- mice, mature single-positive (SP) CD4+ and CD8+ cells were most numerous, at the expense of immature and double-positive (DP) thymocytes. These SP cells also accumulated in the spleen. Human lymphocytes from thymus and spleen were activated, as shown by the expression of CD25: this activation was correlated with the presence of tax mRNA and with increased expression of NF-kB dependent genes such as bfl-1, an anti-apoptotic gene, in thymocytes. Finally, hepato-splenomegaly, lymphadenopathy and lymphoma/thymoma, in which Tax was detected, were observed in HTLV-1-infected mice, several months after HTLV-1 infection. These results demonstrate the potential of the HIS Rag2-/-γc-/- animal model to elucidate the initial steps of the leukemogenic process induced by HTLV-1

ACE2-Mediated Reduction of Oxidative Stress in the Central Nervous System Is Associated with Improvement of Autonomic Function

Oxidative stress in the central nervous system mediates the increase in sympathetic tone that precedes the development of hypertension. We hypothesized that by transforming Angiotensin-II (AngII) into Ang-(1–7), ACE2 might reduce AngII-mediated oxidative stress in the brain and prevent autonomic dysfunction. To test this hypothesis, a relationship between ACE2 and oxidative stress was first confirmed in a mouse neuroblastoma cell line (Neuro2A cells) treated with AngII and infected with Ad-hACE2. ACE2 overexpression resulted in a reduction of reactive oxygen species (ROS) formation. In vivo, ACE2 knockout (ACE2−/y) mice and non-transgenic (NT) littermates were infused with AngII (10 days) and infected with Ad-hACE2 in the paraventricular nucleus (PVN). Baseline blood pressure (BP), AngII and brain ROS levels were not different between young mice (12 weeks). However, cardiac sympathetic tone, brain NADPH oxidase and SOD activities were significantly increased in ACE2−/y. Post infusion, plasma and brain AngII levels were also significantly higher in ACE2−/y, although BP was similarly increased in both genotypes. ROS formation in the PVN and RVLM was significantly higher in ACE2−/y mice following AngII infusion. Similar phenotypes, i.e. increased oxidative stress, exacerbated dysautonomia and hypertension, were also observed on baseline in mature ACE2−/y mice (48 weeks). ACE2 gene therapy to the PVN reduced AngII-mediated increase in NADPH oxidase activity and normalized cardiac dysautonomia in ACE2−/y mice. Altogether, these data indicate that ACE2 gene deletion promotes age-dependent oxidative stress, autonomic dysfunction and hypertension, while PVN-targeted ACE2 gene therapy decreases ROS formation via NADPH oxidase inhibition and improves autonomic function. Accordingly, ACE2 could represent a new target for the treatment of hypertension-associated dysautonomia and oxidative stress