We use observations of dissolved inorganic carbon (DIC)
and total alkalinity (TA) to assess the impact of ecosystem metabolic
processes on coastal waters of the eastern Red Sea. A simple,
...single-end-member mixing model is used to account for the influence of
mixing with offshore waters and evaporation–precipitation and to model
ecosystem-driven perturbations on the carbonate system chemistry of coral
reefs, seagrass meadows and mangrove forests. We find that (1) along-shelf
changes in TA and DIC exhibit strong linear relationships that are
consistent with basin-scale net calcium carbonate precipitation; (2) ecosystem-driven changes in TA and DIC are larger than offshore variations
in >70 % of sampled seagrass meadows and mangrove forests,
changes which are influenced by a combination of longer water residence
times and community metabolic rates; and (3) the sampled mangrove forests
show strong and consistent contributions from both organic respiration and
other sedimentary processes (carbonate dissolution and secondary redox
processes), while seagrass meadows display more variability in the relative
contributions of photosynthesis and other sedimentary processes (carbonate
precipitation and oxidative processes). The results of this study highlight
the importance of resolving the influences of water residence times, mixing
and upstream habitats on mediating the carbonate system and coastal air–sea
carbon dioxide fluxes over coastal habitats in the Red Sea.
Variations in the accumulation rate of barium in marine sediments are thought to be indicative of variations in marine biological productivity through time. However, the use of Ba as a proxy for ...paleoproductivity is partly dependent upon its being preserved in the sediment record in a predictable or consistent fashion. Arguments in favor of high Ba preservation are partly based on the assumption that sediment porewaters are generally at saturation with respect to pure barite. The idea is that because nondetrital sedimentary Ba predominantly exists as barite, porewater saturation would promote burial. We present sediment porewater, sediment solid phase, and benthic incubation chamber data suggesting that solid-phase Ba preservation may be compromised in some geochemical settings. We propose that under suboxic diagenetic conditions, characterized by low bottom water oxygen and high organic carbon respiration rates, Ba preservation may be reduced. Independent of the mechanism, if this assertion is true, then it becomes important to know when the Ba record is unreliable. We present evidence demonstrating that the sedimentary accumulation of authigenic U may serve as a proxy for when the Ba record is unreliable. We then provide an example from the Southern Ocean during the last glacial period where high authigenic U concentrations coincide with high Pa:Th ratios and high accumulation rates of biogenic opal, but we find low accumulation rates of sedimentary Ba. Thus, for the study sites presented here during the last glacial, we conclude that Ba is an unreliable productivity proxy.
The CREB transcription factor regulates differentiation, survival, and synaptic plasticity. The complement of CREB targets responsible for these responses has not been identified, however. We ...developed a novel approach to identify CREB targets, termed serial analysis of chromatin occupancy (SACO), by combining chromatin immunoprecipitation (ChIP) with a modification of SAGE. Using a SACO library derived from rat PC12 cells, we identified ∼41,000 genomic signature tags (GSTs) that mapped to unique genomic loci. CREB binding was confirmed for all loci supported by multiple GSTs. Of the 6302 loci identified by multiple GSTs, 40% were within 2 kb of the transcriptional start of an annotated gene, 49% were within 1 kb of a CpG island, and 72% were within 1 kb of a putative cAMP-response element (CRE). A large fraction of the SACO loci delineated bidirectional promoters and novel antisense transcripts. This study represents the most comprehensive definition of transcription factor binding sites in a metazoan species.
The repressor element 1 (RE1) silencing transcription factor (REST) helps preserve the identity of nervous tissue by silencing neuronal genes in non-neural tissues. Moreover, in an epithelial model ...of tumorigenesis, loss of REST function is associated with loss of adhesion, suggesting the aberrant expression of REST-controlled genes encoding this property. To date, no adhesion molecules under REST control have been identified. Here, we used serial analysis of chromatin occupancy to perform genome-wide identification of REST-occupied target sequences (RE1 sites) in a kidney cell line. We discovered novel REST-binding motifs and found that the number of RE1 sites far exceeded previous estimates. A large family of targets encoding adhesion proteins was identified, as were genes encoding signature proteins of neuroendocrine tumors. Unexpectedly, genes considered exclusively non-neuronal also contained an RE1 motif and were expressed in neurons. This supports the model that REST binding is a critical determinant of neuronal phenotype.
To determine whether a nurse navigator intervention improves quality of life and patient experience with care for people recently given a diagnosis of breast, colorectal, or lung cancer.
Adults with ...recently diagnosed primary breast, colorectal, or lung cancer (n = 251) received either enhanced usual care (n = 118) or nurse navigator support for 4 months (n = 133) in a two-group cluster randomized, controlled trial with primary care physicians as the units of randomization. Patient-reported measures included the Functional Assessment of Cancer Therapy-General (FACT-G) Quality of Life scale, three subscales of the Patient Assessment of Chronic Illness Care (PACIC), and selected subscales from a cancer adaptation of the Picker Institute's patient experience survey. Self-report measures were collected at baseline, 4 months, and 12 months. Automated administrative data were used to assess time to treatment and total health care costs.
There were no significant differences between groups in FACT-G scores. Nurse navigator patients reported significantly higher scores on the PACIC and reported significantly fewer problems with care, especially psychosocial care, care coordination, and information, as measured by the Picker instrument. Cumulative costs after diagnosis did not differ significantly between groups, but lung cancer costs were $6,852 less among nurse navigator patients.
Compared with enhanced usual care, nurse navigator support for patients with cancer early in their course improves patient experience and reduces problems in care, but did not differentially affect quality of life.
The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important ...role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC
values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC
value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects (
= 0.0253) and was treated as a platinum-resistant recurrence. Subsequent gene expression analysis revealed extensively interconnected, differentially expressed pathways related to NF-kB, cellular differentiation (PRDM6 activation), and the linkage of B-cell receptor signaling to the PI3K-Akt signaling pathway (PI3KAP1 activation). This study demonstrates that patient-derived tumor organoids can be developed from patients at the time of primary or interval debulking surgery and may be used to predict clinical platinum sensitivity status or to investigate drivers of carboplatin resistance.
The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 ...children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single-nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort. 224 SNPs were associated with rapid drug clearance or drug resistance, and 32 were replicated in the independent cohort. The adverse risk associated with black and Hispanic ancestries was attenuated by addition of the 4 SNPs most strongly associated with relapse in these populations (for blacks: model without SNPs hazard ratio (HR)=2.32, P=2.27 × 10
, model with SNPs HR=1.07, P=0.79; for Hispanics: model without SNPs HR=1.7, P=8.23 × 10
, model with SNPs HR=1.31, P=0.065). Relapse SNPs associated with asparaginase resistance or allergy were overrepresented among SNPs associated with relapse in the more asparaginase intensive treatment arm (20/54 in Capizzi-methorexate arm vs 8/54 in high-dose methotrexate arm, P=0.015). Inherited genetic variation contributes to race-specific and treatment-specific relapse risk.
Anxiety and depression during pregnancy have been associated with an increased risk of adverse neurodevelopmental outcomes in offspring. We aimed to study the in utero effects of maternal anxiety and ...depression on early brain development.
Pregnant women were recruited at ∼36 weeks of gestation for this prospective study. They were assessed for anxiety symptoms by the State-Trait Anxiety Inventory and for depression symptoms by the Beck Depression Inventory, 2nd Edition. After delivery, infant underwent an MR imaging examination of the brain without sedation, including DTI, for evaluation of white matter (WM) development. Infant fractional anisotropy values, a putative marker of WM integrity, were correlated with the mothers' State-Trait Anxiety Inventory and Beck Depression Inventory scores by using both tract-based spatial statistics and ROI methods.
Thirty-four infants were included in this study. Both maternal State-Anxiety and Trait-Anxiety scores negatively correlated (
< .05, corrected) with fractional anisotropy values in widespread brain WM regions; Beck Depression Inventory scores also negatively correlated (
< .05) with fractional anisotropy values in one cluster in the brain. Further ROI analyses confirmed significant negative correlations between average fractional anisotropy values in ROIs including left and right prefrontal WM, left and right middle frontal gyrus WM, and the fornix, and State-Anxiety (
values, -0.47 to -0.67;
values, .008 to <.001), Trait-Anxiety (R, -0.37 to -0.59;
, .04 to <.001), and Beck Depression Inventory (
values, -0.36 to -0.55;
, .05 to .002) scores.
Higher maternal anxiety and depression symptom scores during late pregnancy were associated with lower estimated infant brain WM development, which indicated in utero influences of maternal mental health during pregnancy on the developing brain.
The oxygen concentration in marine ecosystems is influenced by production and consumption in the water column and fluxes across both the atmosphere–water and benthic–water boundaries. Each of these ...fluxes has the potential to be significant in shallow ecosystems due to high fluxes and low water volumes. This study evaluated the contributions of these three fluxes to the oxygen budget in two contrasting ecosystems, a Zostera marina (eelgrass) meadow in Virginia, U.S.A., and a coral reef in Bermuda. Benthic oxygen fluxes were evaluated by eddy covariance. Water column oxygen production and consumption were measured using an automated water incubation system. Atmosphere–water oxygen fluxes were estimated by parameterizations based on wind speed or turbulent kinetic energy dissipation rates. We observed significant contributions of both benthic fluxes and water column processes to the oxygen mass balance, despite the often-assumed dominance of the benthic communities. Water column rates accounted for 45% and 58% of the total oxygen rate, and benthic fluxes accounted for 23% and 39% of the total oxygen rate in the shallow (~ 1.5 m) eelgrass meadow and deeper (~ 7.5 m) reef site, respectively. Atmosphere–water fluxes were a minor component at the deeper reef site (3%) but a major component at the shallow eelgrass meadow (32%), driven by diel changes in the sign and strength of atmosphere–water gradient. When summed, the measured benthic, atmosphere–water, and water column rates predicted, with 85–90% confidence, the observed time rate of change of oxygen in the water column and provided an accurate, high temporal resolution closure of the oxygen mass balance.
We documented the annual cycle of the carbon isotopic composition of dissolved inorganic carbon (δ13CDIC) in the water columns of the Skagerrak and Baltic Sea to obtain an increased understanding of ...the processes involved controlling the carbon isotopic distribution in shelf seas. The lowest δ13CDIC values (−4.9‰) were found in the low-oxygen, brackish Baltic bottom water whereas the highest values (+1.8‰) were observed in the surface water of the Skagerrak during late summer. Photosynthesis drove the high δ13CDIC values (between 1.0 and 1.8‰) noted in the surface waters of both the Skagerrak and the Baltic. The δ13CDIC values below the halocline in the Baltic reflect mixing of brackish water and the more saline water from the Skagerrak, and foremost organic matter remineralization processes that release significant amounts of low-δ13C CO2. Similarly, in the stagnant fjord basins, little deep water exchange and the degradation of terrestrial and marine organic matter set the δ13C composition. Deep-water renewal in the fjord basins resulted in rapid increases of the δ13CDIC on the order of 1‰, whereas remineralization processes caused a decrease in δ13CDIC of 0.1–0.3‰ per month depending on location. The combined effects of water mixing and remineralization processes (estimated using apparent oxygen utilization (AOU) values) yielded the expression: δ13CDIC=0.032∗S−0.01∗AOU−0.12 for the Baltic – Skagerrak region at water depths below the halocline.
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