Population Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma.

Certepetide (aka LSTA1 and CEND-1) is a novel cyclic tumor-targeting internalizing arginyl glycylaspartic acid peptide being developed to treat solid tumors. Certepetide is designed to overcome existing challenges in treating solid tumors by delivering co-administered anticancer drugs into the tumor while selectively depleting immunosuppressive T cells, enhancing cytotoxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade. A population pharmacokinetic (PK) analysis was conducted to characterize the concentration-time profile of patients with metastatic exocrine pancreatic cancer receiving certepetide in combination with nab-paclitaxel and gemcitabine, and to investigate the effects of clinically relevant covariates on PK parameters.

Synechococcus nitrogen gene loss in iron-limited ocean regions.

Synechococcus are the most abundant cyanobacteria in high latitude regions and are responsible for an estimated 17% of annual marine net primary productivity. Despite their biogeochemical importance, Synechococcus populations have been unevenly sampled across the ocean, with most studies focused on low-latitude strains. In particular, the near absence of Synechococcus genomes from high-latitude, High Nutrient Low Chlorophyll (HNLC) regions leaves a gap in our knowledge of picocyanobacterial adaptations to iron limitation and their influence on carbon, nitrogen, and iron cycles.

Authigenic mineral phases as a driver of the upper-ocean iron cycle.

Iron is important in regulating the ocean carbon cycle. Although several dissolved and particulate species participate in oceanic iron cycling, current understanding emphasizes the importance of complexation by organic ligands in stabilizing oceanic dissolved iron concentrations. However, it is difficult to reconcile this view of ligands as a primary control on dissolved iron cycling with the observed size partitioning of dissolved iron species, inefficient dissolved iron regeneration at depth or the potential importance of authigenic iron phases in particulate iron observational datasets.

BET Bromodomain Degradation Disrupts Function but Not 3D Formation of RNA Pol2 Clusters.

Fusion-positive rhabdomyosarcoma (FP-RMS) is driven by a translocation that creates the chimeric transcription factor PAX3-FOXO1 (P3F), which assembles de novo super enhancers to drive high levels of transcription of other core regulatory transcription factors (CRTFs). P3F recruits co-regulatory factors to super enhancers such as BRD4, which recognizes acetylated lysines via BET bromodomains. In this study, we demonstrate that inhibition or degradation of BRD4 leads to global decreases in transcription, and selective downregulation of CRTFs.

Transport-limited reactions in microbial systems.

Predicting microbial metabolic rates and emergent biogeochemical fluxes remains challenging due to the many unknown population dynamical, physiological and reaction-kinetic parameters and uncertainties in species composition. Here, we show that the need for these parameters can be eliminated when population dynamics and reaction kinetics operate at much shorter time scales than physical mixing processes. Such scenarios are widespread in poorly mixed water columns and sediments.

Corrigendum: Meta-omic signatures of microbial metal and nitrogen cycling in marine oxygen minimum zones.

[This corrects the article DOI: 10.3389/fmicb.2015.

Insights into the bioavailability of oceanic dissolved Fe from phytoplankton uptake kinetics.

Phytoplankton growth in large parts of the world ocean is limited by low availability of dissolved iron (dFe), restricting oceanic uptake of atmospheric CO. The bioavailability of dFe in seawater is however difficult to appraise since it is bound by a variety of poorly characterized organic ligands. Here, we propose a new approach for evaluating seawater dFe bioavailability based on its uptake rate constant by Fe-limited cultured phytoplankton.

Effect of marine antifouling paint particles waste on survival of natural Bermuda copepod communities.

Marine antifouling paints (MAPs) are widely used to prevent organisms from fouling vessel hulls. When scraped from vessels as part of regular maintenance, MAP particles discharged into the seawater become a source of toxic substances, like copper (Cu), to the environment, and biocides leaching from them are known to cause toxic effects on non-target organisms. We investigated the toxicity of MAP particles collected from a Bermuda boatyard on local copepod communities using two experiments.

Pervasive iron limitation at subsurface chlorophyll maxima of the California Current.

Subsurface chlorophyll maximum layers (SCMLs) are nearly ubiquitous in stratified water columns and exist at horizontal scales ranging from the submesoscale to the extent of oligotrophic gyres. These layers of heightened chlorophyll and/or phytoplankton concentrations are generally thought to be a consequence of a balance between light energy from above and a limiting nutrient flux from below, typically nitrate (NO). Here we present multiple lines of evidence demonstrating that iron (Fe) limits or with light colimits phytoplankton communities in SCMLs along a primary productivity gradient from coastal to oligotrophic offshore waters in the southern California Current ecosystem.

The Scientific Legacy of the CARIACO Ocean Time-Series Program.

The CARIACO (Carbon Retention in a Colored Ocean) Ocean Time-Series Program station, located at 10.50°N, 64.66°W, observed biogeochemical and ecological processes in the Cariaco Basin of the southwestern Caribbean Sea from November 1995 to January 2017.

The integral role of iron in ocean biogeochemistry.

The micronutrient iron is now recognized to be important in regulating the magnitude and dynamics of ocean primary productivity, making it an integral component of the ocean's biogeochemical cycles. In this Review, we discuss how a recent increase in observational data for this trace metal has challenged the prevailing view of the ocean iron cycle. Instead of focusing on dust as the major iron source and emphasizing iron's tight biogeochemical coupling to major nutrients, a more complex and diverse picture of the sources of iron, its cycling processes and intricate linkages with the ocean carbon and nitrogen cycles has emerged.

Copper toxicity response influences mesotrophic Synechococcus community structure.

Picocyanobacteria from the genus Synechococcus are ubiquitous in ocean waters. Their phylogenetic and genomic diversity suggests ecological niche differentiation, but the selective forces influencing this are not well defined. Marine picocyanobacteria are sensitive to Cu toxicity, so adaptations to this stress could represent a selective force within, and between, 'species', also known as clades.

Meta-omic signatures of microbial metal and nitrogen cycling in marine oxygen minimum zones.

Iron (Fe) and copper (Cu) are essential cofactors for microbial metalloenzymes, but little is known about the metalloenyzme inventory of anaerobic marine microbial communities despite their importance to the nitrogen cycle. We compared dissolved O2, NO[Formula: see text], NO[Formula: see text], Fe and Cu concentrations with nucleic acid sequences encoding Fe and Cu-binding proteins in 21 metagenomes and 9 metatranscriptomes from Eastern Tropical North and South Pacific oxygen minimum zones and 7 metagenomes from the Bermuda Atlantic Time-series Station. Dissolved Fe concentrations increased sharply at upper oxic-anoxic transition zones, with the highest Fe:Cu molar ratio (1.

Cost of isolation: daily cost of isolation determined and cost avoidance demonstrated from the overuse of personal protective equipment in an acute care facility.

We determined the prevalence and associated cost of isolation precautions. Current census and historic microbiology cultures were assessed for isolation appropriateness following national guidelines. Based on patient assessment and culture data, isolation was discontinued resulting in 4,087 days of isolation and over $141,000 dollars avoided from excess supplies and time.

Developing an early sepsis alert program.

Severe sepsis and septic shock are major health care problems affecting millions of people around the world each year. To aid in early identification and treatment of patients with sepsis, one Midwestern health care system has developed and implemented a computer-assisted sepsis alert system. Despite some limitations, the program has been moderately successful in identifying patients whose condition is declining, and it is having an overall positive effect on patient care.

Phytoplankton responses to atmospheric metal deposition in the coastal and open-ocean Sargasso Sea.

This study investigated the impact of atmospheric metal deposition on natural phytoplankton communities at open-ocean and coastal sites in the Sargasso Sea during the spring bloom. Locally collected aerosols with different metal contents were added to natural phytoplankton assemblages from each site, and changes in nitrate, dissolved metal concentration, and phytoplankton abundance and carbon content were monitored. Addition of aerosol doubled the concentrations of cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), and nickel (Ni) in the incubation water.

The organic complexation of iron in the marine environment: a review.

Iron (Fe) is an essential micronutrient for marine organisms, and it is now well established that low Fe availability controls phytoplankton productivity, community structure, and ecosystem functioning in vast regions of the global ocean. The biogeochemical cycle of Fe involves complex interactions between lithogenic inputs (atmospheric, continental, or hydrothermal), dissolution, precipitation, scavenging, biological uptake, remineralization, and sedimentation processes. Each of these aspects of Fe biogeochemical cycling is likely influenced by organic Fe-binding ligands, which complex more than 99% of dissolved Fe.

Cystatin C and estimated glomerular filtration rate as predictors for adverse outcome in patients with ST-elevation and non-ST-elevation acute coronary syndromes: results from the Platelet Inhibition and Patient Outcomes study.

Background: We evaluated the predictive ability of cystatin C and creatinine-based estimations of glomerular filtration rate (eGFR), including the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, in acute coronary syndrome (ACS) patients with (STE-ACS) or without (NSTE-ACS) ST elevation in a large contemporary ACS population.

Methods: Concentrations of cystatin C and creatinine, as well as eGFR at randomization, were measured in 16 401 patients in the Platelet Inhibition and Patient Outcomes (PLATO) study and evaluated as predictors of the composite end point of cardiovascular death or myocardial infarction within 1 year. Two Cox proportional hazards models were used, the first adjusting for clinical characteristics and the second for clinical characteristics plus the biomarkers N-terminal pro-B-type natriuretic peptide, troponin I, and C-reactive protein.

Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial.

Background: Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates.

Methods And Results: Central laboratory serum creatinine levels were available in 15 202 (81.

Evidence of practice effects in variants of the Trail Making Test during serial assessment.

Practice effects often obscure detection of meaningful intraindividual cognitive change in serial assessment. The Trail Making Test and four of its variants (i.e.

A review of total dissolved copper and its chemical speciation in San Francisco Bay, California.

Following basin-wide contamination from industrial emissions and urban development, total dissolved copper concentrations in some regions of San Francisco Bay have exceeded national and state guidelines for water quality. In the face of dramatic improvements in wastewater treatment and point source control, persisting elevated dissolved copper concentrations in the Bay have prompted multiple studies and extensive monitoring of this estuary since 1989. Statistical analyses of monitoring data show that total dissolved copper concentrations have declined in the North (by 17%) and South (29%) San Francisco Bay as well as in the Southern Sloughs (44%) from 1993 to 2001.