Iron supply has a key role in stimulating phytoplankton blooms in high-nitrate low-chlorophyll oceanic waters. However, the fate of the carbon fixed by these blooms, and how efficiently it is exported into the ocean's interior, remains largely unknown. Here we report on the decline and fate of an iron-stimulated diatom bloom in the Gulf of Alaska. The bloom terminated on day 18, following the depletion of iron and then silicic acid, after which mixed-layer particulate organic carbon (POC) concentrations declined over six days. Increased particulate silica export via sinking diatoms was recorded in sediment traps at depths between 50 and 125 m from day 21, yet increased POC export was not evident until day 24. Only a small proportion of the mixed-layer POC was intercepted by the traps, with more than half of the mixed-layer POC deficit attributable to bacterial remineralization and mesozooplankton grazing. The depletion of silicic acid and the inefficient transfer of iron-increased POC below the permanent thermocline have major implications both for the biogeochemical interpretation of times of greater iron supply in the geological past, and also for proposed geo-engineering schemes to increase oceanic carbon sequestration.
Antimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.
Natural and lab-evolved proteins often recognize their RNA partners with exquisite affinity. Structural analysis of such complexes can offer valuable insight into sequence-selective recognition that can be exploited to alter biological function. Here, we describe the structure of a lab-evolved RNA recognition motif (RRM) bound to the HIV-1 trans-activation response (TAR) RNA element at 1.80 Å-resolution. The complex reveals a trio of arginines in an evolved β2–β3 loop penetrating deeply into the major groove to read conserved guanines while simultaneously forming cation-π and salt-bridge contacts. The observation that the evolved RRM engages TAR within a double-stranded stem is atypical compared to most RRMs. Mutagenesis, thermodynamic analysis and molecular dynamics validate the atypical binding mode and quantify molecular contributions that support the exceptionally tight binding of the TAR-protein complex (KD,App of 2.5 ± 0.1 nM). These findings led to the hypothesis that the β2–β3 loop can function as a standalone TAR-recognition module. Indeed, short constrained peptides comprising the β2–β3 loop still bind TAR (KD,App of 1.8 ± 0.5 μM) and significantly weaken TAR-dependent transcription. Our results provide a detailed understanding of TAR molecular recognition and reveal that a lab-evolved protein can be reduced to a minimal RNA-binding peptide.
Near-surface seawater from the northeastern subarctic Pacific was incubated on deck for 8 d, supplemented with (1) control, no additions (2) ϩZn (3) ϩFe (4) ϩZnϩFe. Concentrations of total Zn and Fe at time zero (t 0 ) and in the control remained at ϳ0.1-0.2 nmol L Ϫ1. In the control, chlorophyll (Ͻ0.3 mg m Ϫ3 ), 14 C uptake into POC and PIC, and inorganic nutrients all remained relatively constant. Addition of Zn slightly but significantly increased chlorophyll (p Ͻ 0.05), decreased phosphate (p Ͻ 0.01) and nitrate (p Ͻ 0.05), and in P versus E experiments, increased P m Ͼ10-fold and P 2-3-fold. The abundance of small diatoms and coccolithophores was higher in the chl m ϩZn treatment compared to the control. The ϩFe and ϩZnϩFe treatments, compared to the control, both showed Ͼ10-fold increases in chlorophyll and 14 C uptake into POC and PIC and complete removal of nitrate (Յ0.2 mmol m Ϫ3 ). However, differences were observed in size-fractionated data; the ϩZnϩFe treatment had significantly lower percent chlorophyll in the Ͼ20-m fraction (p Ͻ 0.01) and a higher percentage in the 0.2-5-m fraction (p Ͻ 0.01) than the ϩFe treatment. In P versus E experiments, both ϩFe treatments increased P m and ␣ around 100-fold and P and ␣ chl by 5-10-fold compared to the control. The ϩFe treatment showed a slightly higher ␣ chl and slightly chl m lower P than the ϩZnϩFe treatment. Abundance of large diatoms, small diatoms, small flagellates, and coccolchl m ithophores all increased substantially (ϳ7-1,000-fold) in response to Fe addition, whereas dinoflagellate abundance only doubled. The ϩZnϩFe treatment had higher abundances of small diatoms and small flagellates than the ϩFe treatment. We conclude that Zn additions had limited influence on conventional indices of phytoplankton growth compared to Fe, but that there might be subtle influences of Zn that require further attention.
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