A multiproxy approach to understanding the "enhanced" flux of organic matter through the oxygen-deficient waters of the Arabian Sea

Free-drifting sediment net traps were deployed 14 times at depths between 80 and 500 m for 1–3 days each during the late monsoon–intermonsoon transition in the central Arabian Sea. Two locations (19.5 and 15.5° N) were within the permanently oxygen-deficient zone (ODZ), and a third (11° N) had a shallow and thin oxygen minimum. The secondary nitrite maximum, which serves as a tracer of the ODZ, thinned from ∼ 250 m thick at stations 19.5 and 15.5° N to ∼ 50 m thick at station 11° N. Overall, organic carbon fluxes ranged from 13.2 g m² yr⁻¹ at 80 m to a minimum of 1.1 g m² yr⁻¹ at 500 m. Fluxes at the more oxygenated 11° N station attenuate faster than within the permanent ODZ. Martin curve attenuation coefficients for 19.5 and 15.5° N are respectively 0.59 and 0.63 and for 11° N it is 0.98. At least six potential mechanisms might explain why particles sinking through the ODZ are more effectively transferred to depth: (M1) oxygen effects, (M2) microbial loop efficiencies and chemoautotrophy, (M3) changes in zooplankton dynamics, (M4) additions of ballast that might sorb and protect organic matter from decay (M4a) or change sinking speeds (M4b), (M5) inputs of refractory organic matter and (M6) temperature effects. These mechanisms are intertwined, and they were explored using a combination of mineral (XPS) and organic matter characterizations of the sinking material, shipboard incubation experiments, and evaluations of existing literature. Direct evidence was found supporting an oxygen effect and/or changes in the efficiency of the microbial loop including the addition of chemoautotrophic carbon to the sinking flux in the upper 500 m. Less direct evidence was found for the other potential mechanisms. A simple conceptual model consistent with our and other recent data suggests that the upper ODZ microbial community determines the initial flux attenuation, and that zooplankton and sinking speed become more important deeper in the water column. The exact interplay between the various mechanisms remains to be further evaluated

A multiproxy approach to understanding the "enhanced" flux of organic matter through the oxygen deficient waters of the Arabian Sea

Abstract. Free-drifting sediment net traps were deployed 14 times at depths between 80 and 500 m for 1–3 days each during the late monsoon/intermonsoon transition in the central Arabian Sea. Two locations (19.5 and 15.5° N) were within the permanently oxygen deficient zone, and a third (11° N) had a shallow and thin oxygen minimum. The secondary nitrite maximum, which serves as a tracer of the oxygen deficient zone (ODZ) zone, thinned from ∼ 250 m thick at stations 19.5 and 15.5° N to ∼ 50 m thick at station 11° N. Overall, organic carbon fluxes ranged from 13.2 g m2 yr−1 at 80 m to a minimum of 1.1 g m2 yr−1 at 500 m. Fluxes at the more oxygenated 11° N station attenuate faster than within the permanent ODZ. Martin curve attenuation coefficients for 19.5 and 15.5° N are 0.59 and 0.63 and for 11° N it is 0.98. At least six potential mechanisms might explain why sinking particles sinking through the ODZ are more effectively transferred to depth; (M1) oxygen effects, (M2) microbial loop efficiencies and chemoautotrophy, (M3) changes in zooplankton dynamics, (M4) additions of ballast that might sorb and protect organic matter from decay, (M5) inputs of refractory organic matter, and (M6) changes in sinking speeds. These mechanisms are intertwined, and were explored using a combination of mineral (XPS) and organic matter characterizations of the sinking material and ship-board incubation experiments. Evidence was found supporting an oxygen effect and/or changes in the efficiency of the microbial loop including the addition of chemoautotrophic carbon to the sinking flux in the upper 500 m. Less evidence was found for the other potential mechanisms. A simple conceptual model consistent with our and other recent data suggests that the upper ODZ microbial community determines the initial flux attenuation, and that deeper in the water column zooplankton and sinking speed become more important. The exact interplay between the various mechanisms remains to be further evaluated.</jats:p

Degradation of Diatom Protein in Seawater: A Peptide-Level View

Peptides and proteins were identified during a controlled laboratory degradation of the marine diatom Thalassiosira weissflogii by a surface seawater microbiome. Samples from each time point were processed both with and without the protease trypsin, allowing a partial differentiation between peptides produced naturally by microbial enzymatic degradation and peptides produced from the laboratory digestion of intact protein. Over the 12-day degradation experiment, 31% of the particulate organic carbon was depleted, and there was no preferential degradation of the overall protein pool. However, there was distinct differentiation in the cellular location, secondary structure and modifications between peptides produced by microbial vs. laboratory breakdown. During the initial period of rapid algal decay and bacterial growth, intracellular components from the cytoplasm were consumed first, resulting in the accumulation of membrane-associated proteins and peptides in the detrital pool. Accompanying the enrichment of membrane protein material was an increase in the importance of ɑ-helix motifs. Methylated arginine, a post-translational modification common in cell senescence, was found in high amounts within the microbially produced detrital peptide pool, suggesting a link between in-cell modification and resistance to immediate degradation. Another modification—asparagine deamidation—accumulated within the detrital peptides. Protein taxonomies showed the bacterial community decomposing the algal material was rich in Proteobacteria, and protein annotations showed abundant transportation of solubilized carbohydrates and small peptides across membranes. At this early stage of diagenesis, no changes in bulk amino acids (THAA) were observed, yet a proteomic approach allowed us to observe selective changes in diatom protein preservation by using amino acid sequences to infer subcellular location, secondary structures, and post-translational modifications (PTMs).</jats:p

Automated Measurement of Plasma Cell-Free Hemoglobin Using the Hemolysis Index Check Function

Abstract Background The Roche Cobas chemistry analyzer’s hemolysis index (HI) check function can directly report hemoglobin (Hb) concentrations. We aimed to validate the HI check function for the measurement of plasma cell-free Hb. Methods Plasma samples (6 μl) were taken by the analyzer and diluted in normal saline to measure the absorbance for Hb at 570 and 600 nm. Hb concentrations were calculated based on the molar extinction coefficient. Imprecision, lower limit of quantification (LLOQ), and analytical measurement range (AMR) of the assay were evaluated. The accuracy was determined by comparing the results between the new method and an existing spectrophotometric method. We further studied interference of icterus and lipemia and carryover. The performance of the assay in proficiency testing was also evaluated. The reference range was transferred from the existing method. Results Within-run and total CVs were 1.7%–4.2% and 2.1%–7.0%, respectively (n = 20). The LLOQ was 11 mg/dL (CV = 8.1%) with the upper limit of AMR of 506 mg/dL. The results of the new method correlated well with the existing reference assay: Y (new method) = 0.974 x (reference method) + 4.9, r = 0.9990, n = 52. Bilirubin with a concentration up to 60 mg/dL and lipemic index up to 389 did not show significant interference. No significant carryover was detected. The average standard deviation index in proficiency testing was 0.03 ± 0.29. The reference range was &amp;lt;22 mg/dL. Conclusions Plasma cell-free Hb measurement using the HI check function meets the analytical requirements of the plasma cell-free Hb assays. It is simple and cost-effective. </jats:sec

Image_7_Degradation of Diatom Protein in Seawater: A Peptide-Level View.pdf

Peptides and proteins were identified during a controlled laboratory degradation of the marine diatom Thalassiosira weissflogii by a surface seawater microbiome. Samples from each time point were processed both with and without the protease trypsin, allowing a partial differentiation between peptides produced naturally by microbial enzymatic degradation and peptides produced from the laboratory digestion of intact protein. Over the 12-day degradation experiment, 31% of the particulate organic carbon was depleted, and there was no preferential degradation of the overall protein pool. However, there was distinct differentiation in the cellular location, secondary structure and modifications between peptides produced by microbial vs. laboratory breakdown. During the initial period of rapid algal decay and bacterial growth, intracellular components from the cytoplasm were consumed first, resulting in the accumulation of membrane-associated proteins and peptides in the detrital pool. Accompanying the enrichment of membrane protein material was an increase in the importance of ɑ-helix motifs. Methylated arginine, a post-translational modification common in cell senescence, was found in high amounts within the microbially produced detrital peptide pool, suggesting a link between in-cell modification and resistance to immediate degradation. Another modification—asparagine deamidation—accumulated within the detrital peptides. Protein taxonomies showed the bacterial community decomposing the algal material was rich in Proteobacteria, and protein annotations showed abundant transportation of solubilized carbohydrates and small peptides across membranes. At this early stage of diagenesis, no changes in bulk amino acids (THAA) were observed, yet a proteomic approach allowed us to observe selective changes in diatom protein preservation by using amino acid sequences to infer subcellular location, secondary structures, and post-translational modifications (PTMs).</p

1360TiP First-line (1L) maintenance therapy with niraparib (nira) + pembrolizumab (pembro) vs placebo + pembro in advanced/metastatic non-small cell lung cancer (NSCLC): Phase III ZEAL-1L study

Background Pembro (programmed death protein 1 [PD-1] inhibitor) ± platinum (Pt)-based chemotherapy (CT), with pembro maintained until progression, is a standard 1L treatment for advanced/metastatic NSCLC. However, durable long-term benefit is limited to a small subset of patients. Nira, a poly(ADP-ribose) polymerase inhibitor (PARPi), promotes PARP trapping, activates the STING pathway, recruits T cells, and upregulates PD-L1, making it a promising partner for PD-1 inhibitors. Nira crosses the blood–brain barrier in animal models with 34-fold higher brain tissue exposure than other PARPi, suggesting it may reduce risk/progression of brain metastasis (BM). Nira + pembro has shown antitumour activity and acceptable safety in triple-negative breast cancer and Pt-resistant ovarian cancer (TOPACIO/KEYNOTE-162), and as 1L therapy in advanced/metastatic NSCLC (JASPER). Trial design ZEAL-1L (NCT04475939) is a phase III, randomised, double-blind trial comparing efficacy and safety of 1L maintenance therapy with oral nira (200/300 mg/day) + intravenous pembro (200 mg on Day 1 of each 21-day cycle; maximum 35 cycles from start of 1L induction CT) versus placebo + pembro in adults with histologically/cytologically confirmed Stage IIIB–IV NSCLC without known driver mutations and with stable disease or partial/complete response to 4–6 cycles of 1L Pt-based induction CT + pembro. Patients with asymptomatic BM (i.e. off corticosteroids and anticonvulsants for ≥7 days) are permitted. Approximately 650 patients will be randomised (1:1), with stratification by histology, PD-L1 status and response to 1L induction CT + pembro. Treatment will continue until disease progression (PD), unacceptable toxicity, death, or loss to follow-up. Imaging occurs every 6 weeks (Q6W) for 48 weeks/until PD, and Q12W for patients still on treatment thereafter. Primary endpoints are PFS and OS. Time to central nervous system progression is a key secondary endpoint; others include investigator-assessed PFS, PFS and OS by PD-L1 status, quality of life, safety and pharmacokinetics. Exploratory analyses are also planned. Enrolment began November 2020. Clinical trial identification NCT04475939. Editorial acknowledgement Medical writing support was provided by Nadia Hashash, PhD, of Core Medica, London, UK, funded by GlaxoSmithKline. Legal entity responsible for the study GlaxoSmithKline. Funding GlaxoSmithKline (ID: 213400)