Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are a novel proxy for mean annual air temperature (MAAT) and have the potential to be broadly applicable to climate reconstruction using ...lacustrine sediments. Several calibrations have been put forth relating brGDGT distributions to MAAT using a variety of linear regressions, including the methylation (MBT) and cyclization (CBT) indices of brGDGTs, the relative abundances of the major, non-cyclized brGDGTs (MbrGDGTs), and best subsets regression (BSR) of the fractional abundances of the nine most common brGDGTs. However, these calibrations have rarely been applied to lake sediment cores to reconstruct temperatures and test the applicability of this proxy as a paleothermometer.
We present an expanded East African lakes surface sediment brGDGT dataset based upon 111 lakes and examine three methods of calibrating brGDGTs to MAAT. These methods include recalculations of the East African lake MBT/CBT calibration and MbrGDGTs calibrations, as well as a new stepwise forward selection (SFS) calibration that uses the four combined brGDGTs that explain the most variance in temperature in our calibration set. We apply these new calibrations as well as five previously published lacustrine brGDGT calibrations to the brGDGT distributions of our surface sediment dataset and a 48kyr sediment core from Sacred Lake, Mt. Kenya, producing the first brGDGT temperature reconstruction available from a small tropical lake. We compare the reconstructed temperatures to previously published paleotemperature records from East Africa to help us assess the performance of the brGDGT calibrations. We find that the SFS calibration has a consistently low root mean squared error of prediction (RMSEP) over the entire range of MAAT, while the MBT/CBT and MbrGDGT calibrations have relatively large RMSEPs, particularly between lakes with similar temperatures but variable pH. This suggests that these techniques do not properly deconvolve the temperature and pH signals recorded in the distributions of the brGDGTs. We further find that only the SFS calibration produces a credible reconstructed temperature history from Sacred Lake when compared to other last glacial maximum paleotemperature estimates from East Africa. Thus, we advocate for the use of the SFS calibration when reconstructing paleotemperatures from brGDGTs in East Africa.
► We examine branched GDGTs in surface sediments in 70 lakes and a single lake core. ► We create three new lacustrine branched GDGT temperature calibrations. ► We compare new and previously published calibrations. ► Only our new calibration deconvolves the pH influence from the temperature signal. ► We present the first branched GDGT temperature record from a small tropical lake.
The Nimbus 7 Limb Infrared Monitor of the Stratosphere (LIMS) instrument
operated from 25 October 1978 through 28 May 1979. This note focuses on
its Version 6 (V6) data and indications of ozone loss ...in the lower
stratosphere of the Southern Hemisphere subpolar region during the last
week of October 1978. We provide profiles and maps that show V6 ozone values
of only 2 to 3 ppmv at 46 hPa within the edge of the polar vortex near
60∘ S from late October through mid-November 1978. There are also
low values of V6 nitric acid (∼3 to 6 ppbv) and nitrogen
dioxide (< 1 ppbv) at the same locations, indicating that conditions
were suitable for a chemical loss of Antarctic ozone some weeks earlier.
These “first light” LIMS observations provide the earliest space-based
view of conditions within the lower stratospheric ozone layer of the
southern polar region in springtime.
Stratospheric Sudden Warmings (SSWs) followed by the formation of an elevated stratopause at ~70–80 km occurred in four of the five recent Arctic winters (2009–2013). We use global high‐latitude ...temperature measurements from the Solar Occultation for Ice Experiment (SOFIE) to analyze the gravity wave (GW) activity in the upper stratosphere and mesosphere (30–90 km) during different phases of the SSW events. We characterize GW activity in terms of temperature fluctuations and the growth of GW potential energy with altitude. At both 40 and 60 km, compared to the non‐SSW year of 2011, the GW activity in the SSW years of 2009, 2010, 2012, and 2013 was reduced after the warming, during the occurrence of an isothermal atmosphere and an elevated stratopause. In contrast, at 80 km the GW activity was highly variable between the individual stratospheric warming events. A case study of GW activity during the 2013 warming event and coincident SOFIE observations of water vapor (H2O) from ~40 to 90 km indicate a correlation between increase in wave activity at each altitude and the time of descent of dry air. This study supports previous modeling studies' findings that enhanced GW activity is responsible for the downward transport of trace species from the mesosphere to the stratosphere following an SSW event.
Key Points
Middle atmospheric gravity wave activity between ~30 and 90 km is calculated
Gravity wave activity is highly variable in the upper mesosphere
Gravity wave activity is enhanced during descent of trace species
The processes that control climate in the tropics are poorly understood. We applied compound-specific hydrogen isotopes (δD) and the TEX₈₆ (tetraether index of 86 carbon atoms) temperature proxy to ...sediment cores from Lake Tanganyika to independently reconstruct precipitation and temperature variations during the past 60,000 years. Tanganyika temperatures follow Northern Hemisphere insolation and indicate that warming in tropical southeast Africa during the last glacial termination began to increase ~3000 years before atmospheric carbon dioxide concentrations. δD data show that this region experienced abrupt changes in hydrology coeval with orbital and millennial-scale events recorded in Northern Hemisphere monsoonal climate records. This implies that precipitation in tropical southeast Africa is more strongly controlled by changes in Indian Ocean sea surface temperatures and the winter Indian monsoon than by migration of the Intertropical Convergence Zone.
Epigenetic alterations, particularly in DNA methylation, are ubiquitous in cancer, yet the molecular origins and the consequences of these alterations are poorly understood. CTCF, a DNA-binding ...protein that regulates higher-order chromatin organization, is frequently altered by hemizygous deletion or mutation in human cancer. To date, a causal role for CTCF in cancer has not been established. Here, we show that Ctcf hemizygous knockout mice are markedly susceptible to spontaneous, radiation-, and chemically induced cancer in a broad range of tissues. Ctcf+/− tumors are characterized by increased aggressiveness, including invasion, metastatic dissemination, and mixed epithelial/mesenchymal differentiation. Molecular analysis of Ctcf+/− tumors indicates that Ctcf is haploinsufficient for tumor suppression. Tissues with hemizygous loss of CTCF exhibit increased variability in CpG methylation genome wide. These findings establish CTCF as a prominent tumor-suppressor gene and point to CTCF-mediated epigenetic stability as a major barrier to neoplastic progression.
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•Mice with hemizygous loss of CTCF are cancer prone•CTCF reduction destabilizes DNA methylation prior to tumor development•CTCF is frequently hemizygously deleted or mutated in human cancer•CTCF is thus a haploinsufficient tumor-suppressor gene
Deletions on chromosome 16q22.1 occur at high frequency in breast and other human cancers, implying the existence of a cancer gene or genes at this location. CTCF, a DNA-binding protein that regulates genome organization, resides at 16q22.1. Kemp et al. now demonstrate that mice lacking one copy of Ctcf have abnormal patterns of DNA methylation and are markedly predisposed to cancer. Furthermore, CTCF is one of the most frequently mutated genes in human cancers, thus establishing CTCF as a major tumor-suppressor gene.
Long-term survival for children with diffuse intrinsic pontine glioma (DIPG) is less than 10%, and new therapeutic targets are urgently required. We evaluated a large cohort of DIPGs to identify ...recurrent genomic abnormalities and gene expression signatures underlying DIPG.
Single-nucleotide polymorphism arrays were used to compare the frequencies of genomic copy number abnormalities in 43 DIPGs and eight low-grade brainstem gliomas with data from adult and pediatric (non-DIPG) glioblastomas, and expression profiles were evaluated using gene expression arrays for 27 DIPGs, six low-grade brainstem gliomas, and 66 nonbrainstem low-grade gliomas.
Frequencies of specific large-scale and focal imbalances varied significantly between DIPGs and nonbrainstem pediatric glioblastomas. Focal amplifications of genes within the receptor tyrosine kinase-Ras-phosphoinositide 3-kinase signaling pathway were found in 47% of DIPGs, the most common of which involved PDGFRA and MET. Thirty percent of DIPGs contained focal amplifications of cell-cycle regulatory genes controlling retinoblastoma protein (RB) phosphorylation, and 21% had concurrent amplification of genes from both pathways. Some tumors showed heterogeneity in amplification patterns. DIPGs showed distinct gene expression signatures related to developmental processes compared with nonbrainstem pediatric high-grade gliomas, whereas expression signatures of low-grade brainstem and nonbrainstem gliomas were similar.
DIPGs comprise a molecularly related but distinct subgroup of pediatric gliomas. Genomic studies suggest that targeted inhibition of receptor tyrosine kinases and RB regulatory proteins may be useful therapies for DIPG.
Using a dynamic graph theoretical approach, Shine et al. show that individuals with Parkinson's disease demonstrate heightened network-level integration during the 'Off' state that is inversely ...correlated with motor symptom severity. Network-level integration relates to two measures of neurocognitive reserve, suggesting a protective function for 'Off' state integration.
Abstract
Parkinson's disease is primarily characterized by diminished dopaminergic function; however, the impact of these impairments on large-scale brain dynamics remains unclear. It has been difficult to disentangle the direct effects of Parkinson's disease from compensatory changes that reconfigure the functional signature of the whole brain network. To examine the causal role of dopamine depletion in network-level topology, we investigated time-varying network structure in 37 individuals with idiopathic Parkinson's disease, both ON and OFF dopamine replacement therapy, along with 50 age-matched, healthy control subjects using resting state functional MRI. By tracking dynamic network-level topology, we found that the Parkinson's disease OFF state was associated with greater network-level integration than in the ON state. The extent of integration in the OFF state inversely correlated with motor symptom severity, suggesting that a shift toward a more integrated network topology may be a compensatory mechanism associated with preserved motor function in the dopamine depleted OFF state. Furthermore, we were able to demonstrate that measures of both cognitive and brain reserve (i.e. premorbid intelligence and whole brain grey matter volume) had a positive relationship with the relative increase in network integration observed in the dopaminergic OFF state. This suggests that each of these factors plays an important role in promoting network integration in the dopaminergic OFF state. Our findings provide a mechanistic basis for understanding the Parkinson's disease OFF state and provide a further conceptual link with network-level reconfiguration. Together, our results highlight the mechanisms responsible for pathological and compensatory change in Parkinson's disease.
CYP2C19 genotype‐guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, ...communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions.
New ionosphere and electrodynamics modules have been incorporated in the thermosphere and ionosphere eXtension of the Whole Atmosphere Community Climate Model (WACCM‐X), in order to self‐consistently ...simulate the coupled atmosphere‐ionosphere system. The first specified dynamics WACCM‐X v.2.0 results are compared with several data sets, and with the Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model (TIE‐GCM), during the deep solar minimum year. Comparisons with Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite of temperature and zonal wind in the lower thermosphere show that WACCM‐X reproduces the seasonal variability of tides remarkably well, including the migrating diurnal and semidiurnal components and the nonmigrating diurnal eastward propagating zonal wavenumber 3 component. There is overall agreement between WACCM‐X, TIE‐GCM, and vertical drifts observed by the Communication/Navigation Outage Forecast System (C/NOFS) satellite over the magnetic equator, but apparent discrepancies also exist. Both model results are dominated by diurnal variations, while C/NOFS observed vertical plasma drifts exhibit strong temporal variations. The climatological features of ionospheric peak densities and heights (NmF2 and hmF2) from WACCM‐X are in general agreement with the results derived from Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) data, although the WACCM‐X predicted NmF2 values are smaller, and the equatorial ionization anomaly crests are closer to the magnetic equator compared to COSMIC and ionosonde observations. This may result from the excessive mixing in the lower thermosphere due to the gravity wave parameterization. These data‐model comparisons demonstrate that WACCM‐X can capture the dynamic behavior of the coupled atmosphere and ionosphere in a climatological sense.
Plain Language Summary
The Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension (WACCM‐X) is a numerical model of entire atmosphere, from the surface to around 600 km in altitude. Recent enhancements to WACCM‐X include a fully coupled ionosphere, including electric field effects and ion transport. WACCM‐X results are compared with several datasets, and with a predecessor, the TIE‐GCM during a very low solar activity year 2008. Comparisons with wind and temperature measurements by the TIMED satellite show that WACCM‐X reproduces the seasonal variability of atmospheric tides remarkably well. There is overall agreement between WACCM‐X, TIE‐GCM, and vertical ion motions observed by the C/NOFS satellite over the magnetic equator, but apparent discrepancies also exist among them. The climatological features of ionospheric peak densities and heights from WACCM‐X are in general agreement with results derived from COSMIC data, although the WACCM‐X‐predicted peak values are smaller, and the equatorial ionosphere has bands of enhancement that are closer to the magnetic equator compared to COSMIC and ionosonde observations. These data‐model comparisons demonstrate that WACCM‐X can capture the basic climate and variation of the coupled atmosphere and ionosphere.
Key Points
First evaluation of WACCM‐X during deep solar minimum year was carried out
Data‐model comparisons illustrate the high fidelity of WACCM‐X
Organic molecular markers determined in a sediment core (V95-1A-1P) from Lake Victoria (East Africa) were used to reconstruct the history of human impact and regional fire activity during the Early ...Iron Age (~2400 to ~1100 yr BP). Fire history was reconstructed using levoglucosan and polycyclic aromatic hydrocarbons (PAHs) as markers for biomass burning that demonstrate two distinct fire periods peaking at 1450–1700 and 1850–2050 cal. yr BP. A partial correlation between levoglucosan and PAHs is interpreted as different transport behaviors and burn temperatures affecting the proxies. A fecal sterol index (CoP-Index) indicates the presence of humans near the lakeshore, where the CoP-Index lags a few centuries behind the fire peaks. The CoP-Index peaks between 1850 and1950 cal. yr BP and between 1400 and 1500 cal. yr BP. Retene, a PAH that indicates softwood combustion, differs from other PAHs and levoglucosan by abruptly increasing at ~1650 cal. yr BP and remaining high until 1200 cal. yr BP. This increase may potentially signal human activity in that the development of metallurgy and/or ceramic production requires highly efficient fuels. However, this increase in retene occurs at the same time as severe drought events centered at ~1500 and ~2000 yr BP where the droughts and associated woodland to grassland transition may have resulted in more intense fires. The grassland expansion could have created favorable conditions for human activities and triggered settlement growth that in turn may have created a positive feedback for further landscape opening.
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