Widespread occurrences of variably crystalline C-13-depleted graphitic carbon in banded iron formations

Almost all evidence for the oldest traces of life on Earth rely on particles of graphitic carbon preserved in rocks of sedimentary protolith. Yet, the source of carbon in such ancient graphite is debated, as it could possibly be non-biological and/or non-indigenous in origin. Here we describe the co-occurrence of poorly crystalline and crystalline varieties of graphitic carbon with apatite in ten different and variably metamorphosed banded iron formations (BIF) ranging in age from 1,800 to >3,800 Myr. In Neoarchean to Palaeoproterozoic BIF subjected to low-grade metamorphism, C-13-depleted graphitic carbon occurs as inclusions in apatite, and carbonate and arguably represents the remineralisation of syngenetic biomass. In BIF subjected to high-grade metamorphism, C-13-depleted graphite co-occurs with poorly crystalline graphite (PCG), as well as apatite, carbonate, pyrite, amphibole and greenalite. Retrograde minerals such as greenalite, and veins cross-cutting magnetite layers contain PCG. Crystalline graphite can occur with apatite and orthopyroxene, and sometimes it has PCG coatings. Crystalline graphite is interpreted to represent the metamorphosed product of syngenetic organic carbon deposited in BIF, while poorly crystalline graphite was precipitated from C-O-H fluids partially sourced from the syngenetic carbon, along with fluid-deposited apatite and carbonate. The isotopic signature of the graphitic carbon and the distribution of fluid-deposited graphite in highly metamorphosed BIF is consistent with carbon in the fluids being derived from the thermal cracking of syngenetic biomass deposited in BIF, but, extraneous sources of carbon cannot be ruled out as a source for PCG. The results here show that apatite + graphite is a common mineral assemblage in metamorphosed BIF. The mode of formation of this assemblage is, however, variable, which has important implications for the timing of life's emergence on Earth. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe

Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo

The mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequencespecific manner to the 3= untranslated regions of many proinflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by the overexpression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent antiinflammatory cytokine interleukin 10 (IL-10). Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of proinflammatory factors via direct or indirect mechanisms. We recently described a knock-in mouse strain in which the substitution of 2 amino acids of the endogenous TTP protein renders it constitutively active as an mRNA-destabilizing factor. Here we investigate the impact on the IL-10-mediated anti-inflammatory response. It is shown that the gain-of-function mutation of TTP impairs IL-10-mediated negative feedback control of macrophage function in vitro. However, the in vivo effects of TTP mutation are uniformly anti-inflammatory despite the decreased expression of IL-10

Long-cavity [Pd2L4]4+ cages and designer 1,8-naphthalimide sulfonate guests: rich variation in affinity and differentiated binding stoichiometry

One of the most appealing features of [Pd2L4]4+ cages is their well-defined cavities, giving binding affinity for specific guests. If seeking to bind larger and more complex guests, an attractive strategy is to lengthen the ligand backbone and therefore the inter-palladium(II) distance and cavity length. In comparison to large hollow [PdnL2n]2n+ polyhedra, this approach retains a well-ordered cavity environment. We report here a novel ligand, 1,3-bis(4-(4-ethynylpyridine)-phenyl)-adamantane, that has a hydrophobic bis(phenyl)adamantane core and forms [Pd2L4]4+ cages with a large 19 Å inter-palladium(II) cavity length. This cage binds long designer anions: naphthalimide sulfonates at ≥15 Å in length, which consist of two distinct domains: a naphthalimide and a phenyl sulfonate. This binding derives from hydrogen bonding between the endohedral pyridyl protons of the cage and the phenyl sulfonate group, and π–hydrophobic interactions between the adamantane core and the naphthalimide unit. The strength of binding depends on the degree of electron deficiency of the naphthalimide, brought about by the nature of substituents on this moiety, with binding constants for monoanionic guests ranging from 400 to 1800 M−1. The host/guest stoichiometry was found to be 1 : 2, unless the guest possessed a second sulfonate group, and was small enough to fit end-to-end within the cavity, in which case the stoichiometry was 1 : 1, and resulted in a high binding constant (for DMSO solvent) of 6100 M−1. This work demonstrates the subtle interplay and potential between cages and guests that are both large and that both have distinct dual zones able to interact with each other, and offers a pathway to specific and tunable binding of large guests.The authors would like to thank the University of Canterbury, the Australian National University, Massey University Albany and the University of Otago for funding. DP, KP and PK would like to thank the MacDiarmid Institute for funding. DP would like to thank the Royal Society of New Zealand for a Rutherford Postdoctoral Fellowship, and the Australian Research Council for a DECRA Fellowship

AGES observations of Abell1367 and its outskirts

The Arecibo Galaxy Environment Survey (AGES, Auld et al. 2006) will map ~200 square degrees over the next years using the ALFA feed array at the 305-m Arecibo Telescope. AGES is specifically designed to investigate various galactic environments from local voids to interacting groups and cluster of galaxies. AGES will map 20 square degrees in the Coma-Abell1367 supercluster including the Abell cluster 1367 and its outskirts (up to ~2 virial radii). In Spring 2006 we nearly completed the observations of 5 square degrees in the range 11:34< RA< 11:54, 19:20<Dec<20:20 covering all the cluster core and part of its infalling region reaching a 5 sigma detection limit of M(HI)~4×10(8)Mxs2299 (assuming a velocity width ~200 km~s(−1)) at the distance of Abell1367 (~92 Mpc). An HI selected sample has been extracted from the datacube obtaining a catalogue of fluxes, recessional velocities, positions and velocity widths. We present a preliminary analysis of the properties of the HI sources and report the discovery of HI diffuse features within interacting groups at the periphery of Abell1367

AGES observations of Abell 1367

We present 21 cm observations of 5×1 square degrees centered on the local Abell cluster 1367 obtained as part of the Arecibo Galaxy Environment Survey. This represents the first HI selected sample covering the core and the outskirts of a local cluster of galaxies. Combining the HI data with SDSS optical imaging we show that in HI selected samples follow scaling relations similar to the ones usually observed in optically selected samples. The most striking difference between HI and optically selected samples resides in their large scale distribution: while optical and X-ray observations trace the cluster potential very well, at radio wavelengths there is almost no evidence of the cluster presence

Emerging role of the calcium-activated, small conductance, SK3 K ⁺ channel in distal tubule function: Regulation by TRPV4

The Ca2+-activated, maxi-K (BK) K+ channel, with low Ca2+-binding affinity, is expressed in the distal tubule of the nephron and contributes to flow-dependent K+ secretion. In the present study we demonstrate that the Ca2+-activated, SK3 (KCa2.3) K + channel, with high Ca2+-binding affinity, is also expressed in the mouse kidney (RT-PCR, immunoblots). Immunohistochemical evaluations using tubule specific markers demonstrate significant expression of SK3 in the distal tubule and the entire collecting duct system, including the connecting tubule (CNT) and cortical collecting duct (CCD). In CNT and CCD, main sites for K+ secretion, the highest levels of expression were along the apical (luminal) cell membranes, including for both principal cells (PCs) and intercalated cells (ICs), posturing the channel for Ca2+- dependent K+ secretion. Fluorescent assessment of cell membrane potential in native, split-opened CCD, demonstrated that selective activation of the Ca2+-permeable TRPV4 channel, thereby inducing Ca2+ influx and elevating intracellular Ca2+ levels, activated both the SK3 channel and the BK channel leading to hyperpolarization of the cell membrane. The hyperpolarization response was decreased to a similar extent by either inhibition of SK3 channel with the selective SK antagonist, apamin, or by inhibition of the BK channel with the selective antagonist, iberiotoxin (IbTX). Addition of both inhibitors produced a further depolarization, indicating cooperative effects of the two channels on Vm. It is concluded that SK3 is functionally expressed in the distal nephron and collecting ducts where induction of TRPV4-mediated Ca2+ influx, leading to elevated intracellular Ca2+ levels, activates this high Ca2+- affinity K+ channel. Further, with sites of expression localized to the apical cell membrane, especially in the CNT and CCD, SK3 is poised to be a key pathway for Ca2+-dependent regulation of membrane potential and K+ secretion. © 2014 Berrout et al

Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism

BACKGROUND. Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess. METHODS. We performed mass spectrometry–based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess. We also analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing adenoma, employing immunohistochemistry with digital image analysis. RESULTS. Primary aldosteronism patients had significantly increased cortisol and total glucocorticoid metabolite excretion (all P < 0.001), only exceeded by glucocorticoid output in patients with clinically overt adrenal Cushing syndrome. Several surrogate parameters of metabolic risk correlated significantly with glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression was significantly associated with the corresponding in vivo glucocorticoid excretion. Unilateral adrenalectomy resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in 13 (29%) of 45 consecutively tested patients. CONCLUSION. Our data indicate that glucocorticoid cosecretion is frequently found in primary aldosteronism and contributes to associated metabolic risk. Mineralocorticoid receptor antagonist therapy alone may not be sufficient to counteract adverse metabolic risk in medically treated patients with primary aldosteronism

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment