Search

The Gram staining method differentiates bacteria based on their cell envelope structure, with the monoderm and diderm cell envelope types traditionally being synonymous with Gram-positive and Gram-negative stain results, respectively. Monoderms have a single phospholipid membrane surrounded by a thick layer of peptidoglycan, while diderms have a lipopolysaccharide outer membrane exterior to a thin peptidoglycan layer. The Bacillota (formerly Firmicutes ) phylum has members with both cell wall types, and recent phylogenetic analyses have shown that monoderm Bacillota evolved from diderm ancestors on multiple occasions. Here, we compiled Gram staining and ultrastructural data for Bacillota species with complete genomes to further investigate the evolution of Gram-positive and Gram-negative cell wall types. The results indicate that many deeply branching lineages at the root of Bacillota phylum stain Gram-negative but do not harbor genes for outer membrane protein or lipopolysaccharide biosynthesis. Phylogenetic reconstructions suggest that several deeply branching Bacillota species have retained a thin peptidoglycan layer in their cell walls, which was inherited from a diderm ancestor. Taxa with this atypical Gram-negative-staining cell wall structure include the thermophilic anaerobe Symbiobacterium thermophilum and members of the Desulfotomaculia, Syntrophamonadia, Desulfitobacteriia, Thermosediminibacteria, and Thermoanaerobacteria . Using Gram-staining results as a proxy for cell wall thickness, our analysis indicates that several independent peptidoglycan thickening events may have occurred in the evolution of the Gram-positive cell envelope., Importance: In this study, we examined the evolution of bacterial cell envelopes, specifically focusing on Gram-positive and Gram-negative cell wall types in the Bacillota phylum. Our results indicate that certain bacteria can stain Gram-negative despite having a monoderm cell wall structure, thus challenging the conventional interpretation of Gram-staining results. Our observations also question the assumption that Gram-negative staining is always indicative of a diderm structure. These findings have broader implications for understanding how and when cell walls thicken during the evolution of bacterial cell envelopes., Competing Interests: The authors declare no conflict of interest.

Microbial reduction of organic disulfides affects the macromolecular structure and chemical reactivity of natural organic matter. Currently, the enzymatic pathways that mediate disulfide bond reduction in soil and sedimentary organic matter are poorly understood. In this study, we examined the extracellular reduction of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) by Shewanella oneidensis strain MR-1. A transposon mutagenesis screen performed with S. oneidensis resulted in the isolation of a mutant that lost ~90% of its DTNB reduction activity. Genome sequencing of the mutant strain revealed that the transposon was inserted into the dsbD gene, which encodes for an oxidoreductase involved in cytochrome c maturation. Complementation of the mutant strain with the wild-type dsbD partially restored DTNB reduction activity. Because DsbD catalyzes a critical step in the assembly of multi-heme c -type cytochromes, we further investigated the role of extracellular electron transfer cytochromes in organic disulfide reduction. The results indicated that mutants lacking proteins in the Mtr system were severely impaired in their ability to reduce DTNB. These findings provide new insights into extracellular organic disulfide reduction and the enzymatic pathways of organic sulfur redox cycling. IMPORTANCE Organic sulfur compounds in soils and sediments are held together by disulfide bonds. This study investigates how Shewanella oneidensis breaks apart extracellular organic sulfur compounds. The results show that an enzyme involved in the assembly of c -type cytochromes as well as proteins in the Mtr respiratory pathway is needed for S. oneidensis to transfer electrons from the cell surface to extracellular organic disulfides. These findings have important implications for understanding how organic sulfur decomposes in terrestrial ecosystems., Competing Interests: The authors declare no conflict of interest.

Copper (Cu) is a cofactor in numerous key proteins and, thus, an essential element for life. In biological systems, Cu isotope abundances shift with metabolic and homeostatic state. However, the mechanisms underpinning these isotopic shifts remain poorly understood, hampering use of Cu isotopes as biomarkers. Computational predictions suggest that isotope fractionation occurs when proteins bind Cu, with the magnitude of this effect dependent on the identity and arrangement of the coordinating amino acids. This study sought to constrain equilibrium isotope fractionation values for Cu bound by common amino acids at protein metal-binding sites. Free and bound metal ions were separated via Donnan dialysis using a cation-permeable membrane. Isotope ratios of pre- and post-dialysis solutions were measured by MC-ICP-MS following purification. Sulfur ligands (cysteine) preferentially bound the light isotope ( 63 Cu) relative to water (Δ 65 Cu complex-free  = - 0.48 ± 0.18‰) while oxygen ligands favored the heavy isotope ( 65 Cu; + 0.26 ± 0.04‰ for glutamate and + 0.16 ± 0.10‰ for aspartate). Binding by nitrogen ligands (histidine) imparted no isotope effect (- 0.01 ± 0.04‰). This experimental work unequivocally demonstrates that amino acids differentially fractionate Cu isotopes and supports the hypothesis that metalloprotein biosynthesis affects the distribution of transition metal isotopes in biological systems., (© 2024. The Author(s).)

Introduction: Pulmonary infections, such as tuberculosis, can result in numerous pleural complications including empyemas, pneumothoraces with broncho-pleural fistulas, and persistent air leak (PAL). While definitive surgical interventions are often initially considered, management of these complications can be particularly challenging if a patient has an active infection and is not a surgical candidate., Case Presentation: Autologous blood patch pleurodesis and endobronchial valve placement have both been described in remedying PALs effectively and safely. PALs due to broncho-pleural fistulas in active pulmonary disease are rare, and we present two such cases that were managed with autologous blood patch pleurodesis and endobronchial valves., Conclusion: The two cases presented illustrate the complexities of PAL management and discuss the treatment options that can be applied to individual patients., (© 2024 S. Karger AG, Basel.)

Of the six elements incorporated into the major polymers of life, phosphorus is the least abundant on a global scale [E. Anders, M. Ebihara, Geochim. Cosmochim. Acta 46, 2363-2380 (1982)] and has been described as the "ultimate limiting nutrient" [T. Tyrrell, Nature 400, 525-531 (1999)]. In the modern ocean, the supply of dissolved phosphorus is predominantly sustained by the oxidative remineralization/recycling of organic phosphorus in seawater. However, in the Archean Eon (4 to 2.5 Ga), surface waters were anoxic and reducing. Here, we conducted photochemical experiments to test whether photodegradation of ubiquitous dissolved organic phosphorus could facilitate phosphorus recycling under the simulated Archean conditions. Our results strongly suggest that organic phosphorus compounds, which were produced by marine biota (e.g., adenosine monophosphate and phosphatidylserine) or delivered by meteorites (e.g., methyl phosphonate) can undergo rapid photodegradation and release inorganic phosphate into solution under anoxic conditions. Our experimental results and theoretical calculations indicate that photodegradation of organic phosphorus could have been a significant source of bioavailable phosphorus in the early ocean and would have fueled primary production during the Archean eon.

With the expansion of research volume, coinciding with the age of the internet, the retraction of published papers from scientific journals has become crucial to preserving scientific integrity. Since the beginning of the COVID-19 pandemic, both public and professional interest in scientific literature has grown as people attempt to educate themselves on the virus. The Retraction Watch Database COVID-19 blog was accessed in June and November of 2022 and analyzed to ensure articles met inclusion criteria. Articles were then accessed on Google Scholar and the Scopus database to find number of citations and SJR/CiteScore. The average SJR and CiteScore for a journal that published one of the articles was 1.531 and 7.3 respectively. The retracted articles were cited an average of 44.8 times, which was significantly higher than the average CiteScore (p = 0.01). Between June and November, retracted COVID-19 articles gained a total of 728 new citations, presence of "withdrawn" or "retracted" before article title did not affect citation rates. COPE guidelines for retraction statements were not met for 32% of articles. We believe retracted COVID-19 publications may have been more likely to include bold claims that garnered a disproportionately high amount of attention within the scientific community. Additionally, we found many journals were not forthright with explanations for why articles had been retracted. Retractions could be a tool used to add to the scientific discourse, but currently we are only getting half the data, the what and not the why., Competing Interests: Conflict of interestAll authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© Akadémiai Kiadó, Budapest, Hungary 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In this study, we investigated Ni 2+ , Zn 2+ , and Co 2+ mineralogical incorporation and its effect on green rust transformation to magnetite. Mineral transformation experiments were conducted by heating green rust suspensions at 85 °C in the presence of Ni 2+ , Zn 2+ , or Co 2+ under strict anoxic conditions. Transmission electron microscopy and powder X-ray diffraction showed the conversion of hexagonal green rust platelets to fine grained cubic magnetite crystals. The addition of Ni 2+ , Zn 2+ , and Co 2+ resulted in faster rates of mineral transformation. The conversion of green rust to magnetite was concurrent to significant increases in metal uptake, demonstrating a strong affinity for metal sorption/co-precipitation by magnetite. Dissolution ratio curves showed that Ni 2+ , Zn 2+ , and Co 2+ cations were incorporated into the mineral structure during magnetite crystal growth. The results indicate that the transformation of green rust to magnetite is accelerated by metal impurities, and that magnetite is a highly effective scavenger of trace metals during mineral transformation. The implications for using diagenetic magnetite from green rust precursors as paleo-proxies of Precambrian ocean chemistry are discussed., (© 2022. The Author(s).)

The Reaction Mechanism Generator (RMG) database for chemical property prediction is presented. The RMG database consists of curated datasets and estimators for accurately predicting the parameters necessary for constructing a wide variety of chemical kinetic mechanisms. These datasets and estimators are mostly published and enable prediction of thermodynamics, kinetics, solvation effects, and transport properties. For thermochemistry prediction, the RMG database contains 45 libraries of thermochemical parameters with a combination of 4564 entries and a group additivity scheme with 9 types of corrections including radical, polycyclic, and surface absorption corrections with 1580 total curated groups and parameters for a graph convolutional neural network trained using transfer learning from a set of >130 000 DFT calculations to 10 000 high-quality values. Correction schemes for solvent-solute effects, important for thermochemistry in the liquid phase, are available. They include tabulated values for 195 pure solvents and 152 common solutes and a group additivity scheme for predicting the properties of arbitrary solutes. For kinetics estimation, the database contains 92 libraries of kinetic parameters containing a combined 21 000 reactions and contains rate rule schemes for 87 reaction classes trained on 8655 curated training reactions. Additional libraries and estimators are available for transport properties. All of this information is easily accessible through the graphical user interface at https://rmg.mit.edu. Bulk or on-the-fly use can be facilitated by interfacing directly with the RMG Python package which can be installed from Anaconda. The RMG database provides kineticists with easy access to estimates of the many parameters they need to model and analyze kinetic systems. This helps to speed up and facilitate kinetic analysis by enabling easy hypothesis testing on pathways, by providing parameters for model construction, and by providing checks on kinetic parameters from other sources.

Saturn's moon Enceladus has a potentially habitable subsurface water ocean that contains canonical building blocks of life (organic and inorganic carbon, ammonia, possibly hydrogen sulfide) and chemical energy (disequilibria for methanogenesis). However, its habitability could be strongly affected by the unknown availability of phosphorus (P). Here, we perform thermodynamic and kinetic modeling that simulates P geochemistry based on recent insights into the geochemistry of the ocean-seafloor system on Enceladus. We find that aqueous P should predominantly exist as orthophosphate (e.g., HPO 4 2- ), and total dissolved inorganic P could reach 10 -7 to 10 -2 mol/kg H 2 O, generally increasing with lower pH and higher dissolved CO 2 , but also depending upon dissolved ammonia and silica. Levels are much higher than <10 -10 mol/kg H 2 O from previous estimates and close to or higher than ∼10 -6 mol/kg H 2 O in modern Earth seawater. The high P concentration is primarily ascribed to a high (bi)carbonate concentration, which decreases the concentrations of multivalent cations via carbonate mineral formation, allowing phosphate to accumulate. Kinetic modeling of phosphate mineral dissolution suggests that geologically rapid release of P from seafloor weathering of a chondritic rocky core could supply millimoles of total dissolved P per kilogram of H 2 O within 10 5 y, much less than the likely age of Enceladus's ocean (10 8 to 10 9 y). These results provide further evidence of habitable ocean conditions and show that any oceanic life would not be inhibited by low P availability.

Sulfur is an essential element of life that is assimilated by Earth's biosphere through the chemical breakdown of pyrite. On the early Earth, pyrite weathering by atmospheric oxygen was severely limited, and low marine sulfate concentrations persisted for much of the Archean eon. Here, we show an anoxic photochemical mechanism of pyrite weathering that could have provided substantial amounts of sulfate to the oceans as continents formed in the late Archean. Pyrite grains suspended in anoxic ferrous iron solutions produced millimolar sulfate concentrations when irradiated with ultraviolet light. The Fe 2+ (aq) was photooxidized, which, in turn, led to the chemical oxidation of pyritic sulfur. Additional experiments conducted with 2.68 Ga shale demonstrated that photochemically derived ferric iron oxidizes and dissolves sedimentary pyrite during chemical weathering. The results suggest that before the rise of atmospheric oxygen, oxidative pyrite weathering on Archean continents was controlled by the exposure of land to sunlight.

► Hematemesis ► History of cirrhosis ► Persistent fevers.

Background: Small airways are known to be affected early in the course of COPD; however, traditional spirometric indices may not accurately identify small airways disease., Research Question: Can forced expiratory volume in 3 s/forced expiratory volume in 6 s (FEV 3 /FEV 6 ) identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD?, Study Design and Methods: The study included 832 current and former smokers with post-bronchodilator FEV 1 /FVC ≥ 0.7 from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Participants were classified as having a reduced pre-bronchodilator FEV 3 /FEV 6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV 3 and FEV 6 . Regression modeling was used to evaluate the relationship between baseline FEV 3 /FEV 6 and outcome measures, including functional small airways disease, on thoracic imaging and respiratory exacerbations. Interval-censored analysis was used to assess progression to COPD., Results: FEV 3 /FEV 6 less than the LLN at baseline, defined as reduced compared with FEV 3 /FEV 6 at or above the LLN, was associated with lower FEV 1 , poorer health status (St. George's Respiratory Questionnaire score), more emphysema, and more functional small airways disease on quantitative imaging. FEV 3 and FEV 6 showed excellent agreement between repeat measurements. A reduced FEV 3 /FEV 6 was associated with increased odds of a severe respiratory exacerbation within the first year of follow-up and decreased time to first exacerbation. A low FEV 3 /FEV 6 was also associated with development of COPD according to spirometry results (post-bronchodilator FEV 1 /FVC < 0.7) during study follow-up., Interpretation: FEV 3 /FEV 6 is a routinely available and repeatable spirometric index that can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV 3 /FEV 6 can identify those at risk for future development of COPD and respiratory exacerbations., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT01969344; URL: www., Clinicaltrials: gov: ClinicalTrials.gov., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

Tellurium (Te) is an emerging contaminant and its chemical transformation in the environment is strongly influenced by microbial processes. In this study, we investigated the adsorption of tellurite [Te(IV), TeO 3 2- ] onto the common soil bacterium Bacillus subtilis . Thiol-blocking experiments were carried out to investigate the role of cell surface sulfhydryl sites in tellurite binding, and extended X-ray absorption fine structure (EXAFS) spectroscopy was performed to determine the chemical speciation of the adsorbed tellurite. The results indicate that tellurite reacts with sulfhydryl functional groups in the extracellular polymeric substances (EPS) produced by B. subtilis . Upon binding to sulfhydryl sites in the EPS, the Te changes from Te-O bonds to Te-S coordination. Further analysis of the surface-associated molecules shows that the EPS of B. subtilis contain proteins. Removal of the proteinaceous EPS dramatically decreases tellurite adsorption and the sulfhydryl surface site concentration. These findings indicate that sulfhydryl binding in EPS plays a key role in tellurite adsorption on bacterial surfaces.

The tellurium oxyanion tellurate is toxic to living organisms even at low concentrations; however, its mechanism of toxicity is poorly understood. Here, we show that exposure of Escherichia coli K-12 to tellurate results in reduction to elemental tellurium (Te[0]) and the formation of intracellular reactive oxygen species (ROS). Toxicity assays performed with E. coli indicated that pre-oxidation of the intracellular thiol pools increases cellular resistance to tellurate-suggesting that intracellular thiols are important in tellurate toxicity. X-ray absorption spectroscopy experiments demonstrated that cysteine reduces tellurate to elemental tellurium. This redox reaction was found to generate superoxide anions. These results indicate that tellurate reduction to Te(0) by cysteine is a source of ROS in the cytoplasm of tellurate-exposed cells., (© 2021. UChicago Argonne, LLC, Operator of Argonne National Laboratory, under exclusive licence to Springer Nature B.V.)

In chemical kinetics research, kinetic models containing hundreds of species and tens of thousands of elementary reactions are commonly used to understand and predict the behavior of reactive chemical systems. Reaction Mechanism Generator (RMG) is a software suite developed to automatically generate such models by incorporating and extrapolating from a database of known thermochemical and kinetic parameters. Here, we present the recent version 3 release of RMG and highlight improvements since the previously published description of RMG v1.0. Most notably, RMG can now generate heterogeneous catalysis models in addition to the previously available gas- and liquid-phase capabilities. For model analysis, new methods for local and global uncertainty analysis have been implemented to supplement first-order sensitivity analysis. The RMG database of thermochemical and kinetic parameters has been significantly expanded to cover more types of chemistry. The present release includes parallelization for faster model generation and a new molecule isomorphism approach to improve computational performance. RMG has also been updated to use Python 3, ensuring compatibility with the latest cheminformatics and machine learning packages. Overall, RMG v3.0 includes many changes which improve the accuracy of the generated chemical mechanisms and allow for exploration of a wider range of chemical systems.

Decreased physical activity (PA) is associated with morbidity and mortality in COPD patients. In this secondary analysis of data from a 12-week longitudinal study, we describe factors associated with PA in COPD. Participants completed the Physical Activity Checklist (PAC) daily for a 7- to 8-day period. PA was measured monthly using the Physical Activity Scale for the Elderly (PASE). At three different time points, daily step count was measured for one week with an Omron HJ-720ITC pedometer. The 35 participants were primarily male (94%) and White (91%), with an average age of 66.5 years and FEV 1 44.9% predicted. Common activities reported on the PAC were walking (93%), preparing a meal (89%), and traveling by vehicle (96%). PA measured by both PASE score ( p = 0.01) and average daily step count ( p = 0.04) decreased during follow-up. In repeated measures multivariable modeling, participants living with others had a higher daily step count (ß = 942 steps, p = 0.01) and better PASE scores (ß = 46.4, p < 0.001). Older age was associated with decreased step count (ß = -77 steps, p < 0.001) whereas White race was associated with lower PASE scores (ß = -55.4, p < 0.001) compared to non-White race. Other demographic factors, quality of life, and medications were not associated with PA. A better understanding of the role of social networks and social support may help develop interventions to improve PA in COPD.

In this study, we investigated the extracellular reactive sulfur species produced by Shewanella oneidensis MR-1 during growth. The results showed that sulfite is the major extracellular sulfur metabolite released to the growth medium under both aerobic and anaerobic growth conditions. Exogenous sulfite at physiological concentrations protected S. oneidensis MR-1 from hydrogen peroxide toxicity and enhanced tolerance to the beta-lactam antibiotics cefazolin, meropenem, doripenem and ertapenem. These findings suggest that the release of extracellular sulfite is a bacterial defence mechanism that plays a role in the mitigation of environmental stress., (© 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.)

A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e. , a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The CAPAC platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans -cyclooctene (TCO)-modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels-Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapies. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33 , as the most promising candidate for in vivo studies. In mice, the maximum tolerated dose (MTD) of SQP33 in combination with locally injected tetrazine-modified biopolymer ( SQL70 ) was determined to be 19.1-times the MTD of conventional doxorubicin. Pharmacokinetics studies in rats show that a single injection of SQL70 efficiently captures multiple SQP33 protodrug doses given cumulatively at 10.8-times the MTD of conventional doxorubicin with greatly reduced systemic toxicity. Finally, combined treatment with SQL70 and SQP33 (together called SQ3370 ) showed antitumor activity in a syngeneic tumor model in mice., Competing Interests: N. A. Yee, S. Srinivasan, A. Mahmoodi, M. Zakharian, and J. M. Mejía Oneto are paid employees and shareholders of Shasqi, Inc. (Shasqi). J. M. Mejía Oneto is the Founder and CEO of Shasqi. M. Royzen is an advisor and shareholder of Shasqi., (This journal is © The Royal Society of Chemistry.)

Anaerobic bacteria are known to produce neurotoxic methylmercury [MeHg] when elemental mercury [Hg(0)] is provided as the sole mercury source. In this study, we examined the formation of MeHg in anaerobic incubations of sediment collected from the San Jacinto River estuary (Texas, USA) amended with aqueous Hg(0) to investigate the microbial communities involved in the conversion of Hg(0) to MeHg. The results show that the addition of the methanogen inhibitor 2-bromoethanesulfonate (BES) significantly decreased MeHg production. The mercury methylation gene, hgcA, was detected in these sediments using archaeal specific primers, and 16S rRNA sequencing showed that a member of the Methanosarcinaceae family of methanogens was active. These results suggest that methanogenic archaea play an underappreciated role in the production of MeHg in estuarine sediments contaminated with Hg(0)., (© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.)

Bio-derived isobutanol has been approved as a gasoline additive in the US, but our understanding of its combustion chemistry still has significant uncertainties. Detailed quantum calculations could improve model accuracy leading to better estimation of isobutanol's combustion properties and its environmental impacts. This work examines 47 molecules and 38 reactions involved in the first oxygen addition to isobutanol's three alkyl radicals located α, β, and γ to the hydroxide. Quantum calculations are mostly done at CCSD(T)-F12/cc-pVTZ-F12//B3LYP/CBSB7, with 1-D hindered rotor corrections obtained at B3LYP/6-31G(d). The resulting potential energy surfaces are the most comprehensive isobutanol peroxy networks published to date. Canonical transition state theory and a 1-D microcanonical master equation are used to derive high-pressure-limit and pressure-dependent rate coefficients, respectively. At all conditions studied, the recombination of γ-isobutanol radical with O 2 forms HO 2 + isobutanal. The recombination of β-isobutanol radical with O 2 forms a stabilized hydroperoxy alkyl radical below 400 K, water + an alkoxy radical at higher temperatures, and HO 2 + an alkene above 1200 K. The recombination of β-isobutanol radical with O 2 results in a mixture of products between 700-1100 K, forming acetone + formaldehyde + OH at lower temperatures and forming HO 2 + alkenes at higher temperatures. The barrier heights, high-pressure-limit rates, and pressure-dependent kinetics generally agree with the results from previous quantum chemistry calculations. Six reaction rates in this work deviate by over three orders of magnitude from kinetics in detailed models of isobutanol combustion, suggesting the rates calculated here can help improve modeling of isobutanol combustion and its environmental fate.

The oxidation states of manganese minerals in the geological record have been interpreted as proxies for the evolution of molecular oxygen in the Archean eon. Here we report that an Archean manganese mineral, rhodochrosite (MnCO 3 ), can be photochemically oxidized by light under anoxic, abiotic conditions. Rhodochrosite has a calculated bandgap of about 5.4 eV, corresponding to light energy centering around 230 nm. Light at that wavelength would have been present on Earth's surface in the Archean, prior to the formation of stratospheric ozone. We show experimentally that the photooxidation of rhodochrosite in suspension with light centered at 230 nm produced H 2 gas and manganite (γ-MnOOH) with an apparent quantum yield of 1.37 × 10 -3 moles hydrogen per moles incident photons. Our results suggest that manganese oxides could have formed abiotically on the surface in shallow waters and on continents during the Archean eon in the absence of molecular oxygen., Competing Interests: The authors declare no competing interest.

Background: Frailty is a complex clinical syndrome associated with vulnerability to adverse health outcomes. While frailty is thought to be common in chronic obstructive pulmonary disease (COPD), the relationship between frailty and COPD-related outcomes such as risk of acute exacerbations of COPD (AE-COPD) and hospitalizations is unclear., Purpose: To examine the association between physical frailty and risk of acute exacerbations, hospitalizations, and mortality in patients with COPD., Methods: A longitudinal analysis of data from a cohort of 280 participants was performed. Baseline frailty measures included exhaustion, weakness, low activity, slowness, and undernutrition. Outcome measures included AE-COPD, hospitalizations, and mortality over 2 years. Negative binomial regression and Cox proportional hazard modeling were used., Results: Sixty-two percent of the study population met criteria for pre-frail and 23% were frail. In adjusted analyses, the frailty syndrome was not associated with COPD exacerbations. However, among the individual components of the frailty syndrome, weakness measured by handgrip strength was associated with increased risk of COPD exacerbations (IRR 1.46, 95% CI 1.09-1.97). The frailty phenotype was not associated with all-cause hospitalizations but was associated with increased risk of non-COPD-related hospitalizations., Conclusion: This longitudinal cohort study shows that a high proportion of patients with COPD are pre-frail or frail. The frailty phenotype was associated with an increased risk of non-COPD hospitalizations but not with all-cause hospitalizations or COPD exacerbations. Among the individual frailty components, low handgrip strength was associated with increased risk of COPD exacerbations over a 2-year period. Measuring handgrip strength may identify COPD patients who could benefit from programs to reduce COPD exacerbations., Competing Interests: Some of these results were previously presented as an abstract. Yee N, Locke ER, Nguyen HQ, Fan VS Frailty in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acute Exacerbations. D104 phenotypes and the multiple dimensions of COPD. p. A7497-A7497. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. Vincent Fan reports grants from VA BLR&D, VA HSR&D, VA Cooperative Studies Program, Firland Foundation, VA RR&D, and PCORI, during the conduct of the study. The authors report no other possible conflicts of interest in this work., (© 2020 Yee et al.)

An efficient general methodology for the synthesis of 4-quinolinyl ethers is demonstrated via a highly reactive S N Ar reaction of 4-quinolinyl sulfones with a range of structurally diversified 1°, 2°, and 3° alcohols with a wide substrate scope and high yields. By adapting this methodology, a convergent synthesis of a complex target of HCV NS3/4a protease inhibitor BI 201420 was accomplished.

Firocoxib (ML-1,785,713) is a nonsteroidal, potent, and selective COX-2 inhibitor, approved for the control of pain and inflammation associated with osteoarthritis in dogs and horses, as well as to control postoperative pain and inflammation in dogs. We employed a six-step synthesis to prepare firocoxib-[ 13 C 6 ] in an overall yield of 35% from the commercially available bromobenzene-[ 13 C 6 ]. The synthetic route involved the preparation of the key intermediate phenyl- 13 C 6 -methyl sulfide using cesium carbonate and S-methylthiourea sulfate under transition-metal free conditions. A two-step preparation of firocoxib-[ 13 C, 2 H 3 ] via the sulfinic acid derivative of firocoxib and methyl iodide-[ 13 C, 2 H 3 ] using the procedure of Gauthier and Yoshikawa was first undertaken. However, the deuterium atoms of the methyl sulfone undergo extensive exchange in aqueous media even at neutral pH. The isotope-labelled firocoxib is intended as an internal standard for bioanalyses of firocoxib from biological matrices., (© 2020 John Wiley & Sons, Ltd.)

5-Cyanoimidazole was identified as an inexpensive ligand for nickel-catalyzed cross-electrophile couplings by screening a diverse set of pharmaceutical compound library. A strategic screening approach led to the discovery of this novel ligand, which was successfully applied in the preparation of various alkylated arene products with good to high yields. Furthermore, the properties of this ligand allowed expanding the scope of reductive couplings to challenging substrates, such as sterically hindered neopentyl halides, which are known to generate motifs that are prevalent in biologically active molecules.

We report the serendipitous discovery and synthesis of an indigoid "semi-Nindigo" ( 2 ) via oxidation of a diindolopyrrole ( 1 ). The reaction of 2 with BF 3 Et 2 O affords the borylated derivative ( 3 ). The electronic spectra of 2 and 3 possess intense long wave absorptions near 600 and 650 nm. Compound 3 is weakly emissive in the near-infrared. Thin-film OFETs fabricated with 1 and 2 both exhibited hole mobility of 10 -5 and 10 -3 cm 2 /(V s), respectively.

A series of new dihydrobenzooxophosphole-based Lewis Base organocatalysts were designed and synthesized. They are demonstrated effective in trichlorosilane-mediated stereoselective conjugate reductions of C=C bonds. DFT calculations reveal that the strong hydrogen bond between the amide linker and the chloride on silicon in the transition state contributes to the high reactivity of the catalyst 3a .

The incorporation of metal cofactors into protein active sites and/or active regions expanded the network of microbial metabolism during the Archean eon. The bioavailability of crucial metal cofactors is largely influenced by earth surface redox state, which impacted the timing of metabolic evolution. Vanadium (V) is a unique element in geo-bio-coevolution due to its complex redox chemistry and specific biological functions. Thus, the extent of microbial V utilization potentially represents an important link between the geo- and biospheres in deep time. In this study, we used geochemical modeling and network analysis to investigate the availability and chemical speciation of V in the environment, and the emergence and changing chemistry of V-containing minerals throughout earth history. The redox state of V shifted from a more reduced V(III) state in Archean aqueous geochemistry and mineralogy to more oxidized V(IV) and V(V) states in the Proterozoic and Phanerozoic. The weathering of vanadium sulfides, vanadium alkali metal minerals, and vanadium alkaline earth metal minerals were potential sources of V to the environment and microbial utilization. Community detection analysis of the expanding V mineral network indicates tectonic and redox influence on the distribution of V mineral-forming elements. In reducing environments, energetic drivers existed for V to potentially be involved in early nitrogen fixation, while in oxidizing environments vanadate ( VO 4 3 - ] ] > ) could have acted as a metabolic electron acceptor and phosphate mimicking enzyme inhibitor. The coevolving chemical speciation and biological functions of V due to earth's changing surface redox conditions demonstrate the crucial links between the geosphere and biosphere in the evolution of metabolic electron transfer pathways and biogeochemical cycles from the Archean to Phanerozoic., (© 2020 John Wiley & Sons Ltd.)

The Joint Workshop on Induced Special Regions convened scientists and planetary protection experts to assess the potential of inducing special regions through lander or rover activity. An Induced Special Region is defined as a place where the presence of the spacecraft could induce water activity and temperature to be sufficiently high and persist for long enough to plausibly harbor life. The questions the workshop participants addressed were: (1) What is a safe stand-off distance, or formula to derive a safe distance, to a purported special region? (2) Questions about RTGs (Radioisotope Thermoelectric Generator), other heat sources, and their ability to induce special regions. (3) Is it possible to have an infected area on Mars that does not contaminate the rest of Mars? The workshop participants reached a general consensus addressing the posed questions, in summary: (1) While a spacecraft on the surface of Mars may not be able to explore a special region during the prime mission, the safe stand-off distance would decrease with time because the sterilizing environment, that is the martian surface would progressively clean the exposed surfaces. However, the analysis supporting such an exploration should ensure that the risk to exposing interior portions of the spacecraft (i.e., essentially unsterilized) to the martian surface is minimized. (2) An RTG at the surface of Mars would not create a Special Region but the short-term result depends on kinetics of melting, freezing, deliquescence, and desiccation. While a buried RTG could induce a Special Region, it would not pose a long-term contamination threat to Mars, with the possible exception of a migrating RTG in an icy deposit. (3) Induced Special Regions can allow microbial replication to occur (by definition), but such replication at the surface is unlikely to globally contaminate Mars. An induced subsurface Special Region would be isolated and microbial transport away from subsurface site is highly improbable., (Copyright © 2019. Published by Elsevier Ltd.)

The dissolution of elemental selenium [Se(0)] during chemical weathering is an important step in the global selenium cycle. While microorganisms have been shown to play a key role in selenium dissolution in soils, the mechanisms of microbial selenium solubilization are poorly understood. In this study, we isolated a Bacillus species, designated as strain JG17, that exhibited the ability to dissolve Se(0) under oxic conditions and neutral pH. Growth of JG17 in a defined medium resulted in the production and accumulation of extracellular compounds that mediated Se(0) dissolution. Analysis of the spent medium revealed the presence of extracellular sulfite, sulfide, and thiosulfate. Abiotic Se(0) dissolution experiments with concentrations of sulfite, sulfide, and thiosulfate relevant to our system showed similar extents of selenium solubilization as the spent medium. Together, these results indicate that the solubilization of Se(0) by JG17 occurs via the release of extracellular inorganic sulfur compounds followed by chemical dissolution of Se(0) by the reactive sulfur metabolites. Our findings suggest that the production of reactive sulfur metabolites by soil microorganisms and the formation of soluble selenosulfur complexes can promote selenium mobilization during chemical weathering., (© 2018 John Wiley & Sons Ltd.)

The application of a Buchwald's third generation palladacycle containing a dihydrobenzooxaphosphole-based ligand (e.g., BIDIME) was reported in the Suzuki cross-coupling reaction. Using flow technology, high yield and reproducible Suzuki cross-coupling reaction for one of our key intermediates was achieved with Pd loadings as low as 0.5 mol %. This continuous flow approach overcomes catalyst deactivation and scale dependence issues that can be a problem in some traditional batch-mode operations and responds to the challenge of improving process greenness.

Systemic administration of antibiotics can cause severe side-effects such as liver and kidney toxicity, destruction of healthy gut bacteria, as well as multidrug resistance. Here, we present a bio-orthogonal chemistry-based strategy toward local prodrug concentration and activation. The strategy is based on the inverse electron-demand Diels-Alder chemistry between trans -cyclooctene and tetrazine and involves a biomaterial that can concentrate and activate multiple doses of systemic antibiotic therapy prodrugs at a local site. We demonstrate that a biomaterial, consisting of alginate hydrogel modified with tetrazine, is efficient at activating multiple doses of prodrugs of vancomycin and daptomycin in vitro as well as in vivo . These results support a drug delivery process that is independent of endogenous environmental markers. This approach is expected to improve therapeutic efficacy with decreased side-effects of antibiotics against bacterial infections. The platform has a wide scope of possible applications such as wound healing, and cancer and immunotherapy., Competing Interests: The authors declare the following competing financial interest(s): Jose M. Mejia Oneto is the founder of Shasqi, Inc. Nathan A. Yee and Sangeetha Srinivasan are employed by Shasqi, Inc. Its core technology is based on the research described herein.

The anaerobic bacterium Geobacter bemidijensis Bem has the unique ability to both produce and degrade methylmercury (MeHg). While the adsorption of MeHg onto bacterial surfaces can affect the release of MeHg into aquatic environments as well as the uptake of MeHg for demethylation, the binding of MeHg to the bacterial envelope remains poorly understood. In this study, we quantified the adsorption of MeHg onto G. bemidijensis and applied X-ray absorption spectroscopy (XAS) to elucidate the mechanism of MeHg binding. The results showed MeHg adsorption onto G. bemidijensis cell surfaces was rapid and occurred via complexation to sulfhydryl functional groups. Titration experiments yielded cell surface sulfhydryl concentrations of 3.8 ± 0.2 μmol/g (wet cells). A one-site adsorption model with MeHg binding onto sulfhydryl sites provided excellent fits to adsorption isotherms conducted at different cell densities. The log K binding constant of MeHg onto the sulfhydryl sites was determined to be 10.5 ± 0.4. These findings provide a quantitative framework to describe MeHg binding onto bacterial cell surfaces and elucidate the importance of bacterial cells as possible carriers of adsorbed MeHg in natural aquatic systems.

The C9H11 potential energy surface (PES) was experimentally and theoretically explored because it is a relatively simple, prototypical alkylaromatic radical system. Although the C9H11 PES has already been extensively studied both experimentally (under single-collision and thermal conditions) and theoretically, new insights were made in this work by taking a new experimental approach: flash photolysis combined with time-resolved molecular beam mass spectrometry (MBMS) and visible laser absorbance. The C9H11 PES was experimentally accessed by photolytic generation of the phenyl radical and subsequent reaction with excess propene (C6H5 + C3H6). The overall kinetics of C6H5 + C3H6 was measured using laser absorbance with high time-resolution from 300 to 700 K and was found to be in agreement with earlier measurements over a lower temperature range. Five major product channels of C6H5 + C3H6 were observed with MBMS at 600 and 700 K, four of which were expected: hydrogen (H)-abstraction (measured by the stable benzene, C6H6, product), methyl radical (CH3)-loss (styrene detected), H-loss (phenylpropene isomers detected) and radical adduct stabilization. The fifth, unexpected product observed was the benzyl radical, which was rationalized by the inclusion of a previously unreported pathway on the C9H11 PES: aromatic-catalysed 1,2-H-migration and subsequent resonance stabilized radical (RSR, benzyl radical in this case) formation. The current theoretical understanding of the C9H11 PES was supported (including the aromatic-catalyzed pathway) by quantitative comparisons between modelled and experimental MBMS results. At 700 K, the branching to styrene + CH3 was 2-4 times greater than that of any other product channel, while benzyl radical + C2H4 from the aromatic-catalyzed pathway accounted for ∼10% of the branching. Single-collision conditions were also simulated on the updated PES to explain why previous crossed molecular beam experiments did not see evidence of the aromatic-catalyzed pathway. This experimentally validated knowledge of the C9H11 PES was added to the database of the open-source Reaction Mechanism Generator (RMG), which was then used to generalize the findings on the C9H11 PES to a slightly more complicated alkylaromatic system.

This work presents kinetic modeling efforts to evaluate the anti-knock tendency of several substituted phenols if used as gasoline additives. They are p-cresol, m-cresol, o-cresol, 2,4-xylenol, 2-ethylphenol, and guaiacol. A detailed kinetic model was constructed to predict the ignition of blends of the phenols in n-butane with the help of reaction mechanism generator (RMG), an open-source software package. The resulting model, which has 1465 species and 27 428 reactions, was validated against literature n-butane ignition data in the low-to-intermediate temperature range. To rank the anti-knock tendency of the additives, engine-like simulations were performed in a closed adiabatic homogenous batch reactor with a volume history derived from the pressure profile of a real research octane number (RON) engine test. The ignition timings of the additive blends were compared to that of primary reference fuels (PRFs) to quantitatively predict the anti-knock ability. The model predictions agree well with experimental determinations of the changes in RON induced by the additives. This study explains the chemical mechanism by which methyl-substituted phenols increase RON, and demonstrates how fundamental chemical kinetics can be used to evaluate practical fuel additive performance.

A new class of tunable heterophosphole dimeric ligands have been designed and synthesized. These ligands have enabled the first examples of Cu-catalyzed hydrogenation of 2-substituted-1-tetralones and related heteroaryl ketones via dynamic kinetic resolution, simultaneously creating two contiguous stereogenic centers with up to >99 : 1 dr and 98 : 2 er. The ligand-Cu complexes were isolated and characterized by single crystal X-ray, and DFT calculations revealed a novel heteroligated dimeric copper hydride transition state.

Novel bidentate phosphine ligands BABIPhos featuring a biaryl bis-dihydrobenzooxaphosphole core are presented. Their synthesis was achieved via Pd-catalyzed reductive homocoupling of dihydrobenzooxaphosphole aryl triflates. An efficient route toward various analogues was also established, giving access to phosphines with different electronic and steric properties. The newly obtained ligands demonstrated high efficiency and selectivity in Rh-catalyzed asymmetric hydrogenation of di- and trisubstituted enamides. This new class of ligands is complementary to previously described bidentate benzooxaphosphole ligands BIBOP.

Enantioselective synthesis of α-aryl and α-heteroaryl piperidines is reported. The key step is an iridium-catalyzed asymmetric hydrogenation of substituted N-benzylpyridinium salts. High levels of enantioselectivity up to 99.3:0.7 er were obtained for a range of α-heteroaryl piperidines. DFT calculations support an outersphere dissociative mechanism for the pyridinium reduction. Notably, initial protonation of the final enamine intermediate determines the stereochemical outcome of the transformation rather than hydride reduction of the resultant iminium intermediate.

A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).

Soluble forms of tellurium are environmental contaminants that are toxic to microorganisms. While tellurite [Te(IV)] is a well-characterized antimicrobial agent, little is known about the interactions of tellurate [Te(VI)] with bacterial cells. In this study, we investigated the role of sulfate transporters in the uptake of tellurate in Escherichia coli K-12. Mutant strains carrying a deletion of the cysW gene in the CysPUWA sulfate transporter system accumulated less cellular tellurium and exhibited higher resistance to tellurate compared with the wild-type strain. Complementation of the mutation restored tellurate sensitivity and uptake. These results indicate that tellurate enters E. coli cells to cause toxic effects via the CysPUWA sulfate transporter., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The development of enantioselective carbon-carbon bond couplings catalyzed by nonprecious metals is highly desirable in terms of cost efficiency and sustainability. The first nickel-catalyzed enantioselective Mizoroki-Heck coupling is reported. This transformation is accomplished via mild reaction conditions, leveraging on QuinoxP* as a chiral ligand to afford oxindoles containing quaternary stereocenters. Good reactivity and selectivity are observed in the presence of various functional groups. Computational studies suggest that the oxidative addition assembles an atropisomeric intermediate responsible for the facial selectivity of the insertion step.

An efficient and practical synthesis of enantiomerically pure P-chiral dihydrobenzooxaphosphole (BOP) core 1 is developed that is amenable to large scale preparation of the related ligand series. The unique epimerization of the P-chiral center of the undesired (R,R)-diastereomeric phosphine oxide 19 through chlorination followed by crystallization makes this chemical resolution method achieve 65% yield of desired (R,S)-diastereomer 12.

Molybdoenzymes are an ancient protein family found in phylogenetically and ecologically diverse prokaryotes. Under anaerobic conditions, respiratory molybdoenzymes catalyze redox reactions that transfer electrons to a variety of substrates that act as terminal electron acceptors for energy generation. Here, we used probe sequences to conduct an extensive genomic survey and phylogenetic inference for NarG, DmsA, TorA and nine other respiratory molybdoenzyme subfamilies. Our analysis demonstrates their abundance in 60% of prokaryotic phyla. In contrast to many other autonomic genetic units in prokaryotes, the major route of evolution of their predominant subfamilies is vertical gene transfer, gene duplication and divergence. Our results show the robustness of genomic co-occurrence of respiratory molybdoenzymes genes, found in the majority of studied species, for most of the enzyme subfamilies. Genomes which encode for multiple respiratory molybdoenzymes are also enriched in genes regulating replication, recombination and mobility of genetic elements. Respiratory molybdoenzymes were found in prokaryotes associated with diverse environments occupying terrestrial, aquatic, food and host-related habitats, emphasizing their essential role in adaptation of prokaryotes to changing environments. Interestingly, host-associated prokaryotes such as human pathogens more frequently carry multiple respiratory molybdoenzyme genes compared with non-host-associated prokaryotes, highlighting the importance of metabolic flexibility in host-microbiome environments., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A concise asymmetric synthesis of an 11β-HSD-1 inhibitor has been achieved using inexpensive starting materials with excellent step-economy at low catalyst loadings. The catalytic enantioselective total synthesis of 1 was accomplished in 7 steps and 38% overall yield aided by the development of an innovative, sequential strategy involving Pd-catalyzed pyridinium C-H arylation and Ir-catalyzed asymmetric hydrogenation of the resulting fused tricyclic indenopyridinium salt highlighted by the use of a unique P,N-ligand (MeO-BoQPhos) with 1000 ppm of [Ir(COD)Cl] 2 .

The disposal of elemental mercury (Hg(0)) wastes in mining and manufacturing areas has caused serious soil and groundwater contamination issues. Under anoxic conditions, certain anaerobic bacteria can oxidize dissolved elemental mercury and convert the oxidized Hg to neurotoxic methylmercury. In this study, we conducted experiments with the Hg-methylating bacterium Desulfovibrio desulfuricans ND132 to elucidate the role of cellular thiols in anaerobic Hg(0) oxidation. The concentrations of cell-surface and intracellular thiols were measured, and specific fractions of D. desulfuricans ND132 were examined for Hg(0) oxidation activity and analyzed with extended X-ray absorption fine structure (EXAFS) spectroscopy. The experimental data indicate that intracellular thiol concentrations are approximately six times higher than those of the cell wall. Cells reacted with a thiol-blocking reagent were severely impaired in Hg(0) oxidation activity. Spheroplasts lacking cell walls rapidly oxidized Hg(0) to Hg(II), while cell wall fragments exhibited low reactivity toward Hg(0). EXAFS analysis of spheroplast samples revealed that multiple different forms of Hg-thiols are produced by the Hg(0) oxidation reaction and that the local coordination environment of the oxidized Hg changes with reaction time. The results of this study indicate that Hg(0) oxidation in D. desulfuricans ND132 is an intracellular process that occurs by reaction with thiol-containing molecules.

An Ir-catalyzed enantioselective hydrogenation of 2-alkyl-pyridines has been developed using ligand MeO-BoQPhos. High levels of enantioselectivities up to 93:7 er were obtained. The resulting enantioenriched piperidines can be readily converted into biologically interesting molecules such as the fused tricyclic structures 5, 6, and 7 in 99:1 er, providing a novel, concise synthetic route to this family of chiral piperidine-containing compounds.