Seawater isotope constraints on tropical hydrology during the Holocene

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 34 (2007): L13701, doi:10.1029/2007GL030017.Paleoceanographic data from the low latitude Pacific Ocean provides evidence of changes in the freshwater budget and redistribution of freshwater within the basin during the Holocene. Reconstructed Holocene seawater δ 18O changes compare favorably to differences predicted between climate simulations for the middle Holocene (MH) and for the pre-Industrial late Holocene (LH). The model simulations demonstrate that changes in the tropical hydrologic cycle affect the relationship between δ 18Osw and surface salinity, and allow, for the first time, quantitative estimates of western Pacific salinity change during the Holocene. The simulations suggest that during the MH, the mean salinity of the Pacific was higher because less water vapor was transported from the Atlantic Ocean and more was transported to the Indian Ocean. The salinity of the western Pacific was enhanced further due both to the greater advection of salt to the region by ocean currents and to an increase in continental precipitation at the expense of maritime precipitation, the latter a consequence of the stronger Asian summer monsoon.This work was supported by NSF grants ATM-0501241, ATM-0501351, and WHOI’s Ocean and Climate Change Institute

p16INK4a-induced senescence is disabled by melanoma-associated mutations

The p16INK4a-Rb tumour suppressor pathway is required for the initiation and maintenance of cellular senescence, a state of permanent growth arrest that acts as a natural barrier against cancer progression. Senescence can be overcome if the pathway is not fully engaged, and this may occur when p16INK4a is inactivated. p16INK4a is frequently altered in human cancer and germline mutations affecting p16INK4a have been linked to melanoma susceptibility. To characterize the functions of melanoma-associated p16INK4a mutations, in terms of promoting proliferative arrest and initiating senescence, we utilized an inducible expression system in a melanoma cell model. We show that wild-type p16INK4a promotes rapid cell cycle arrest that leads to a senescence programme characterized by the appearance of chromatin foci, activation of acidic β-galactosidase activity, p53 independence and Rb dependence. Accumulation of wild-type p16INK4a also promoted cell enlargement and extensive vacuolization independent of Rb status. In contrast, the highly penetrant p16INK4a variants, R24P and A36P failed to arrest cell proliferation and did not initiate senescence. We also show that overexpression of CDK4, or its homologue CDK6, but not the downstream kinase, CDK2, inhibited the ability of wild-type p16INK4a to promote cell cycle arrest and senescence. Our data provide the first evidence that p16INK4a can initiate a CDK4/6-dependent autonomous senescence programme that is disabled by inherited melanoma-associated mutations

A limited role for unforced internal variability in 20th century warming.

The early twentieth-century warming (EW; 1910–45) and the mid-twentieth-century cooling (MC; 1950–80) have been linked to both internal variability of the climate system and changes in external radiative forcing. The degree to which either of the two factors contributed to EW and MC, or both, is still debated. Using a two-box impulse response model, we demonstrate that multidecadal ocean variability was unlikely to be the driver of observed changes in global mean surface temperature (GMST) after AD 1850. Instead, virtually all (97%–98%) of the global low-frequency variability (.30 years) can be explained by external forcing. We find similarly high percentages of explained variance for interhemispheric and land–ocean temperature evolution. Three key aspects are identified that underpin the conclusion of this new study: inhomogeneous anthropogenic aerosol forcing (AER), biases in the instrumental sea surface temperature (SST) datasets, and inadequate representation of the response to varying forcing factors. Once the spatially heterogeneous nature of AER is accounted for, the MC period is reconcilable with external drivers. SST biases and imprecise forcing responses explain the putative disagreement between models and observations during the EW period. As a consequence, Atlantic multidecadal variability (AMV) is found to be primarily controlled by external forcing too. Future attribution studies should account for these important factors when discriminating between externally forced and internally generated influences on climate. We argue that AMV must not be used as a regressor and suggest a revised AMV index instead [the North Atlantic Variability Index (NAVI)]. Our associated best estimate for the transient climate response (TCR) is 1.57 K (60.70 at the 5%–95% confidence level)

Towards a realistic population of simulated galaxy groups and clusters

We present a new suite of large-volume cosmological hydrodynamical simulations called cosmo-OWLS. They form an extension to the OverWhelmingly Large Simulations (OWLS) project, and have been designed to help improve our understanding of cluster astrophysics and non-linear structure formation, which are now the limiting systematic errors when using clusters as cosmological probes. Starting from identical initial conditions in either the Planck or WMAP7 cosmologies, we systematically vary the most important ‘sub-grid’ physics, including feedback from supernovae and active galactic nuclei (AGN). We compare the properties of the simulated galaxy groups and clusters to a wide range of observational data, such as X-ray luminosity and temperature, gas mass fractions, entropy and density profiles, Sunyaev–Zel'dovich flux, I-band mass-to-light ratio, dominance of the brightest cluster galaxy and central massive black hole (BH) masses, by producing synthetic observations and mimicking observational analysis techniques. These comparisons demonstrate that some AGN feedback models can produce a realistic population of galaxy groups and clusters, broadly reproducing both the median trend and, for the first time, the scatter in physical properties over approximately two decades in mass (1013 M⊙ ≲ M500 ≲ 1015 M⊙) and 1.5 decades in radius (0.05 ≲ r/r500 ≲ 1.5). However, in other models, the AGN feedback is too violent (even though they reproduce the observed BH scaling relations), implying that calibration of the models is required. The production of realistic populations of simulated groups and clusters, as well as models that bracket the observations, opens the door to the creation of synthetic surveys for assisting the astrophysical and cosmological interpretation of cluster surveys, as well as quantifying the impact of selection effects

Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming

A strong connection exists between the cell cycle and mechanisms required for executing cell fate decisions in a wide-range of developmental contexts. Terminal differentiation is often associated with cell cycle exit, whereas cell fate switches are frequently linked to cell cycle transitions in dividing cells. These phenomena have been investigated in the context of reprogramming, differentiation and trans-differentiation but the underpinning molecular mechanisms remain unclear. Most progress to address the connection between cell fate and the cell cycle has been made in pluripotent stem cells, in which the transition through mitosis and G1 phase is crucial for establishing a window of opportunity for pluripotency exit and the initiation of differentiation. This Review will summarize recent developments in this area and place them in a broader context that has implications for a wide range of developmental scenarios

Gothic Revival Architecture Before Horace Walpole's Strawberry Hill

The Gothic Revival is generally considered to have begun in eighteenth-century Britain with the construction of Horace Walpole’s villa, Strawberry Hill, Twickenham, in the late 1740s. As this chapter demonstrates, however, Strawberry Hill is in no way the first building, domestic or otherwise, to have recreated, even superficially, some aspect of the form and ornamental style of medieval architecture. Earlier architects who, albeit often combining it with Classicism, worked in the Gothic style include Sir Christopher Wren, Nicholas Hawksmoor, William Kent and Batty Langley, aspects of whose works are explored here. While not an exhaustive survey of pre-1750 Gothic Revival design, the examples considered in this chapter reveal how seventeenth- and eighteenth-century Gothic emerged and evolved over the course of different architects’ careers, and how, by the time that Walpole came to create his own Gothic ‘castle’, there was already in existence in Britain a sustained Gothic Revivalist tradition

The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2.

The two distinct proteins encoded by the CDKN2A locus are specified by translating the common second exon in alternative reading frames. The product of the alpha transcript, p16(INK4a), is a recognized tumour suppressor that induces a G1 cell cycle arrest by inhibiting the phosphorylation of the retinoblastoma protein by the cyclin-dependent kinases, CDK4 and CDK6. In contrast, the product of the human CDKN2A beta transcript, p14(ARF), activates a p53 response manifest in elevated levels of MDM2 and p21(CIP1) and cell cycle arrest in both G1 and G2/M. As a consequence, p14(ARF)-induced cell cycle arrest is p53 dependent and can be abrogated by the co-expression of human papilloma virus E6 protein. p14(ARF) acts by binding directly to MDM2, resulting in the stabilization of both p53 and MDM2. Conversely, p53 negatively regulates p14(ARF) expression and there is an inverse correlation between p14(ARF) expression and p53 function in human tumour cell lines. However, p14(ARF) expression is not involved in the response to DNA damage. These results place p14(ARF) in an independent pathway upstream of p53 and imply that CDKN2A encodes two proteins that are involved in tumour suppression