Cluster size dependent coordination of formate to free manganese oxide clusters.

The interaction of free manganese oxide clusters, MnxOy+ (x = 1-9, y = 0-12), with formic acid was studied via infrared multiple-photon dissociation (IR-MPD) spectroscopy together with calculations using density functional theory (DFT). Clusters containing only one Mn atom, such as MnO2+ and MnO4+, bind formic acid as an intact molecule in both the cis- and trans-configuration. In contrast, all clusters containing two or more manganese atoms deprotonate the acid's hydroxyl group. The coordination of the resulting formate group is strongly cluster-size-dependent according to supporting DFT calculations for selected model systems. For Mn2O2+ the co-existence of two isomers with the formate bound in a bidentate bridging and chelating configurations, respectively, is found, whereas for Mn2O4+ the bidentate chelating configuration is preferred. In contrast, the bidentate bridging structure is energetically considerably more favorable for Mn4O4+. This binding motif stabilizes the 2D ring structure of the core of the Mn4O4+ cluster with respect to the 3D cubic geometry of the Mn4O4+ cluster core.

Constraining the contribution of the Antarctic Ice Sheet to Last Interglacial sea level.

Polar temperatures during the Last Interglacial [LIG; ~129 to 116 thousand years (ka)] were warmer than today, making this time period an important testing ground to better understand how ice sheets respond to warming. However, it remains debated how much and when the Antarctic and Greenland ice sheets changed during this period. Here, we present a combination of new and existing absolutely dated LIG sea-level observations from Britain, France, and Denmark. Because of glacial isostatic adjustment (GIA), the LIG Greenland ice melt contribution to sea-level change in this region is small, which allows us to constrain Antarctic ice change. We find that the Antarctic contribution to LIG global mean sea level peaked early in the interglacial (before 126 ka), with a maximum contribution of 5.7 m (50th percentile, 3.6 to 8.7 m central 68% probability) before declining. Our results support an asynchronous melt history over the LIG, with an early Antarctic contribution followed by later Greenland Ice Sheet mass loss.

Spin-Gated Selectivity of the Water Oxidation Reaction Mediated by Free Pentameric CaxMn5-xO5+ Clusters.

We report on the first preparation of isolated ligand-free CaMn4O5+ gas-phase clusters, as well as other pentameric CaxMn5-xO5+ (x = 0-4) clusters with varying Ca contents, which serve as molecular models of the natural CaMn4O5 inorganic cluster in photosystem II. Ion trap reactivity studies with D2O and H218O reveal a pronounced cluster composition-dependent ability to mediate the oxidation of water to hydrogen peroxide. First-principles density functional theory simulations elucidate the mechanism of water oxidation, proceeding via formation of a terminal oxyl radical followed by oxyl/hydroxy (O/OH) coupling. The critical coupling reaction step entails a single electron transfer from the oxyl radical to the accommodating cluster core with a concurrent O/OH coupling forming an adsorbed OOH intermediate group. The spin-conserving electron transfer step takes place when the spin of the transferred electron is aligned with the spins of the d-electrons of the Mn atoms in the cuboidal high-spin cluster isomer. The d-electrons provide a ferromagnetically ordered environment that facilitates the spin-gated selective electron transfer process, resulting in parallel-spin-exchange stabilization and a lowered transition state barrier for the coupling reaction involving the frontier orbitals of the oxyl and hydroxy reactant intermediates.

Low-salinity transitions drive abrupt microbial response to sea-level change.

The salinisation of many coastal ecosystems is underway and is expected to continue into the future because of sea-level rise and storm intensification brought about by the changing climate. However, the response of soil microbes to increasing salinity conditions within coastal environments is poorly understood, despite their importance for nutrient cascading, carbon sequestration and wider ecosystem functioning. Here, we demonstrate deterioration in the productivity of a top-tier microbial group (testate amoebae) with increasing coastal salinity, which we show to be consistent across phylogenetic groups, salinity gradients, environment types and latitude. Our results show that microbial changes occur in the very early stages of marine inundation, presaging more radical changes in soil and ecosystem function and providing an early warning of coastal salinisation that could be used to improve coastal planning and adaptation.

Room-Temperature Methane Activation Mediated by Free Tantalum Cluster Cations: Size-by-Size Reactivity.

The energetics of small cationic tantalum clusters and their gas-phase adsorption and dehydrogenation reaction pathways with methane are investigated with ion-trap experiments and spin-density-functional-theory calculations. Tan+ clusters are exposed to methane under multicollision conditions in a cryogenic ring electrode ion-trap. The cluster size affects the reaction efficiency and the number of consecutively dehydrogenated methane molecules. Small clusters (n = 1-4) dehydrogenate CH4 and concurrently eliminate H2, while larger clusters (n > 4) demonstrate only molecular adsorption of methane. Unique behavior is found for the Ta+ cation, which dehydrogenates consecutively up to four CH4 molecules and is predicted theoretically to promote formation of a [Ta(CH2-CH2-CH2)(CH2)]+ product, exhibiting C-C coupled groups. Underlying mechanisms, including reaction-enhancing couplings between potential energy surfaces of different spin-multiplicities, are uncovered.

Size, Stoichiometry, Dimensionality, and Ca Doping of Manganese Oxide-Based Water Oxidation Clusters: An Oxyl/Hydroxy Mechanism for Oxygen-Oxygen Coupling.

Gas-phase ion-trap reactivity experiments and density functional simulations reveal that water oxidation to H2O2 mediated by (calcium) manganese oxide clusters proceeds via formation of a terminal oxyl radical followed by oxyl/hydroxy O-O coupling. This mechanism is predicted to be energetically feasible for Mn2Oy+ (y = 2-4) and the binary CaMn3O4+, in agreement with the experimental observations. In contrast, the reaction does not proceed for the tetramanganese oxides Mn4Oy+ (y = 4-6) under these experimental conditions. This is attributed to the high fluxionality of the tetramanganese clusters, resulting in the instability of the terminal oxyl radical as well as an energetically unfavorable change of the spin state required for H2O2 formation. Ca doping, yielding a symmetry-broken lower-symmetry three-dimensional (3D) CaMn3O4+ cluster, results in structural stabilization of the oxyl radical configuration, accompanied by a favorable coupling between potential energy surfaces with different spin states, thus enabling the cluster-mediated water oxidation reaction and H2O2 formation.

Cluster Size Dependent Interaction of Free Manganese Oxide Clusters with Acetic Acid and Methyl Acetate.

We have employed infrared multiple-photon dissociation (IR-MPD) spectroscopy together with density functional theory (DFT) calculations to study the interaction of series of subnanometer sized manganese oxide clusters, MnxOy+ (x = 1-6, y = 0-9) with acetic acid (HOAc) and methyl acetate (MeOAc). Reaction with HOAc leads to strongly cluster size and composition dependent IR-MPD spectra, indicating molecular adsorption on MnOx+ clusters and thermodynamically favorable but kinetically hampered HOAc dissociation (deprotonation) on Mn2O4+ and Mn3O5+. Other cluster sizes exhibit the preferred formation of a dissociative bidentate chelating structure. In contrast to HOAc, all clusters bind MeOAc via the carbonyl group as an intact molecule, and dissociation appears to be kinetically hindered under the given experimental conditions.

Rest tremor correlates with reduced contralateral striatal dopamine transporter binding in Parkinson's disease.

INTRODUCTION: In vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor. However, while many of the motoric features of Parkinson's disease (e.g. bradykinesia, rigidity, hypomimia) correlate well with reduced striatal dopamine transporter binding, the same relationship has not been demonstrated for tremor. We investigated the relationship between striatal dopamine transporter binding and quantitative measures of tremor. METHODS: 23 participants with Parkinson's disease underwent standardised clinical assessment including structured, videotaped clinical examination, tremor neurophysiology study of both upper limbs using accelerometry and surface EMG, and Technitium-99 m TRODAT-1 brain SPECT imaging. Normalised striatal uptake values were calculated. Tremor EMG and accelerometry time series were processed with Fourier transformation to identify peak tremor power within a window of 3-10Hz and to calculate the tremor stability index (TSI). RESULTS: Spearman correlation analyses revealed an association between tremor power and contralaterally reduced striatal uptake in a number of recording conditions. This association was strongest for rest tremor, followed by postural tremor, with the weakest association observed for kinetic tremor. Lower TSI was also associated with lower contralateral striatal uptake in a number of rest and postural conditions. CONCLUSION: These data suggest a relationship between Parkinsonian rest tremor and contralateral reduction in striatal dopamine binding. Use of quantitative neurophysiology techniques may allow the demonstration of clinico-pathophysiological relationships in tremor that have remained occult to previous studies.

Nonlinear landscape and cultural response to sea-level rise.

Rising sea levels have been associated with human migration and behavioral shifts throughout prehistory, often with an emphasis on landscape submergence and consequent societal collapse. However, the assumption that future sea-level rise will drive similar adaptive responses is overly simplistic. While the change from land to sea represents a dramatic and permanent shift for preexisting human populations, the process of change is driven by a complex set of physical and cultural processes with long transitional phases of landscape and socioeconomic change. Here, we use reconstructions of prehistoric sea-level rise, paleogeographies, terrestrial landscape change, and human population dynamics to show how the gradual inundation of an island archipelago resulted in decidedly nonlinear landscape and cultural responses to rising sea levels. Interpretation of past and future responses to sea-level change requires a better understanding of local physical and societal contexts to assess plausible human response patterns in the future.

Carbide Dihydrides: Carbonaceous Species Identified in Ta4 + -Mediated Methane Dehydrogenation.

The products of methane dehydrogenation by gas-phase Ta4 + clusters are structurally characterized using infrared multiple photon dissociation (IRMPD) spectroscopy in conjunction with quantum chemical calculations. The obtained spectra of [4Ta,C,2H]+ reveal a dominance of vibrational bands of a H2 Ta4 C+ carbide dihydride structure over those indicative for a HTa4 CH+ carbyne hydride one, as is unambiguously verified by studies employing various methane isotopologues. Because methane dehydrogenation by metal cations M+ typically leads to the formation of either MCH2 + carbene or HMCH+ carbyne hydride structures, the observation of a H2 MC+ carbide dihydride structure implies that it is imperative to consider this often-neglected class of carbonaceous intermediates in the reaction of metals with hydrocarbons.

Comparative Assessments of Left and Right Ventricular Function by Two-Dimensional, Contrast Enhanced and Three-Dimensional Echocardiography with Gated Heart Pool Scans in Patients Following Myocardial Infarction.

Multiple noninvasive imaging modalities are available to measure biventricular function, although limited studies have assessed agreement between modalities in assessing left and right ventricular ejection fraction (LVEF & RVEF) in the same cohort of patients. In this study we prospectively compared the agreement of 2-dimensional echocardiography (2DE), contrast enhanced 2DE, 3-dimensional echocardiography (3DE), and gated heart pool scan (GHPS) measures of LVEF and RVEF in patients with acute ST-elevation myocardial infarction. We recruited 95 consecutive ST-elevation myocardial infarction patients (mean age 61.4 ± 12.0, male: 79.5%) admitted to a major tertiary hospital between July 2016 and May 2018. Despite minimal inter- and intra-observer variability (coefficient of variance < 5% in both categories), substantial discrepancies exist between modalities with Pearson's correlation coefficients ranging from 0.64 to 0.91 for LVEF measurements, and 0.27 to 0.86 for RVEF measurements. Bland-Altman plots demonstrated no systematic bias between modalities. GHPS and 3DE offered the closest agreement for both LVEF and RVEF, demonstrating the greatest correlation coefficient (r = 0.91 and 0.86 respectively), lowest mean absolute differences (4% and 3% respectively), and narrowest Bland-Altman limits of agreement (19% and 18% respectively). Greater than 10% of 2DE and contrast enhanced 2DE scans discordantly showed LVEF values >40% for patients whose LVEF was measured as ≤ 40% by 3DE or GHPS. In conclusion, substantial variation exists between modalities when assessing LVEF and RVEF, although we demonstrate that 3DE and GHPS have the closest agreement. This variability should be considered in clinical management of patients, and modalities should not be used interchangeably in sequential patient follow-up.

Energetic Stabilization of Carboxylic Acid Conformers by Manganese Atoms and Clusters.

Free cationic manganese atoms and clusters Mnx+ (x = 1-3) have been reacted with small carboxylic acids (formic, acetic, and propionic acids) and methyl acetate in a flow tube reactor held at room temperature. The geometry of the thus formed complexes has subsequently been studied via infrared multiple-photon dissociation (IR-MPD) spectroscopy and density-functional theory (DFT) calculations. The IR-MPD spectra of the acid complexes show two signals in the C═O stretch region indicating the coexistence of two conformers. In agreement, the DFT calculations reveal that the-intrinsically less stable-cis-conformer of the carboxylic acids binds more strongly to Mn+ than the trans-conformer, which leads to the energetic stabilization of the former. This stronger binding is attributed to a stronger electrostatic interaction with the manganese cation. A similar stabilization is also predicted for the cis-conformer of methyl acetate; however, the resulting change of the C═O stretch eigenfrequency is too small to be resolved in the experiment. This finding can open up completely new routes for the future room-temperature preparation of the cis-conformers of carboxylic acids and their derivatives.

Infrared Spectroscopy of Gas-Phase MnxOy(CO2)z+ Complexes.

The interaction of manganese oxide clusters MnxOy+ (x = 2-5, y ≥ x) with CO2 is studied via infrared multiple-photon dissociation spectroscopy (IR-MPD) in the spectral region of 630-1860 cm-1. Along with vibrational modes of the manganese oxide cluster core, two bands are observed around 1200-1450 cm-1 and they are assigned to the characteristic Fermi resonance of CO2 arising from anharmonic coupling between the symmetric stretch vibration and the overtone of the bending mode. The spectral position of the lower frequency band depends on the cluster size and the number of adsorbed CO2 molecules, whereas the higher frequency band is largely unaffected. Despite these effects, the observation of the Fermi dyad indicates only a small perturbation of the CO2 molecule. This finding is confirmed by the theoretical investigation of Mn2O2(CO2)+ revealing only small orbital mixing between the dimanganese oxide cluster and CO2, indicative of mainly electrostatic interaction.

Disruption of Membrane Integrity by the Bacterium-Derived Antifungal Jagaricin.

Jagaricin is a lipopeptide produced by the bacterial mushroom pathogen Janthinobacterium agaricidamnosum, the causative agent of mushroom soft rot disease. Apart from causing lesions in mushrooms, jagaricin is a potent antifungal active against human-pathogenic fungi. We show that jagaricin acts by impairing membrane integrity, resulting in a rapid flux of ions, including Ca2+, into susceptible target cells. Accordingly, the calcineurin pathway is required for jagaricin tolerance in the fungal pathogen Candida albicans Transcriptional profiling of pathogenic yeasts further revealed that jagaricin triggers cell wall strengthening, general shutdown of membrane potential-driven transport, and the upregulation of lipid transporters, linking cell envelope integrity to jagaricin action and resistance. Whereas jagaricin shows hemolytic effects, it exhibited either no or low plant toxicity at concentrations at which the growth of prevalent phytopathogenic fungi is inhibited. Therefore, jagaricin may have potential for agricultural applications. The action of jagaricin as a membrane-disrupting antifungal is promising but would require modifications for use in humans.

A Gas-Phase Can Mn4-n O4+ Cluster Model for the Oxygen-Evolving Complex of Photosystem II.

One of the fundamental processes in nature, the oxidation of water, is catalyzed by a small CaMn3 O4 ⋅MnO cluster located in photosystem II (PS II). Now, the first successful preparation of a series of isolated ligand-free tetrameric Can Mn4-n O4+ (n=0-4) cluster ions is reported, which are employed as structural models for the catalytically active site of PS II. Gas-phase reactivity experiments with D2 O and H218 O in an ion trap reveal the facile deprotonation of multiple water molecules via hydroxylation of the cluster oxo bridges for all investigated clusters. However, only the mono-calcium cluster CaMn3 O4+ is observed to oxidize water via elimination of hydrogen peroxide. First-principles density functional theory (DFT) calculations elucidate mechanistic details of the deprotonation and oxidation reactions mediated by CaMn3 O4+ as well as the role of calcium.

The legacy of 4,500 years of polyculture agroforestry in the eastern Amazon.

The legacy of pre-Columbian land use in the Amazonian rainforest is one of the most controversial topics in the social1-10 and natural sciences11,12. Until now, the debate has been limited to discipline-specific studies, based purely on archaeological data8, modern vegetation13, modern ethnographic data3 or a limited integration of archaeological and palaeoecological data12. The lack of integrated studies to connect past land use with modern vegetation has left questions about the legacy of pre-Columbian land use on the modern vegetation composition in the Amazon, unanswered11. Here, we show that persistent anthropogenic landscapes for the past 4,500 years have had an enduring legacy on the hyperdominance of edible plants in modern forests in the eastern Amazon. We found an abrupt enrichment of edible plant species in fossil lake and terrestrial records associated with pre-Columbian occupation. Our results demonstrate that, through closed-canopy forest enrichment, limited clearing for crop cultivation and low-severity fire management, long-term food security was attained despite climate and social changes. Our results suggest that, in the eastern Amazon, the subsistence basis for the development of complex societies began ~4,500 years ago with the adoption of polyculture agroforestry, combining the cultivation of multiple annual crops with the progressive enrichment of edible forest species and the exploitation of aquatic resources. This subsistence strategy intensified with the later development of Amazonian dark earths, enabling the expansion of maize cultivation to the Belterra Plateau, providing a food production system that sustained growing human populations in the eastern Amazon. Furthermore, these millennial-scale polyculture agroforestry systems have an enduring legacy on the hyperdominance of edible plants in modern forests in the eastern Amazon. Together, our data provide a long-term example of past anthropogenic land use that can inform management and conservation efforts in modern Amazonian ecosystems.

The Chemoattractant Glorin Is Inactivated by Ester Cleavage during Early Multicellular Development of Polysphondylium pallidum.

Among the amoebozoan species capable of forming fruiting bodies, the dictyostelid social amoebae stand out since they form true multicellular organisms by means of single cell aggregation. Upon food depletion, cells migrate across gradients of extracellular signals initiated by cells in aggregation centers. The model species that is widely used to study multicellular development of social amoebae, Dictyostelium discoideum, uses cyclic adenosine monophosphate (cAMP) as a chemoattractant to coordinate aggregation. Molecular phylogeny studies suggested that social amoebae evolved in four major groups, of which groups 1 and 2 are paraphyletic to groups 3 and 4. During early development, intercellular communication with cAMP appears to be restricted to group 4 species. Cells of group 1 and 2 taxa do not respond chemotactically to extracellular cAMP and likely use a dipeptide chemoattractant known as glorin ( N-propionyl-γ-L-glutamyl-L-ornithin-δ-lactam-ethylester) to regulate aggregation. Directional migration of glorin-responsive cells requires the periodic breakdown of the chemoattractant. Here, we identified an extracellular enzymatic activity (glorinase) in the glorin-responsive group 2 taxon Polysphondylium pallidum leading to the inactivation of glorin. We determined the inactivation mechanism to proceed via hydrolytic ethyl ester cleavage of the γ-glutamyl moiety of glorin. Synthetic glorinamide, in which the ethyl ester group was substituted by an ethyl amide group, had glorin-like biological activity but was resistant to degradation by glorinase. Our observations pave the way for future investigations toward an ancient eukaryotic chemotaxis system.

Thermal stability of iron-sulfur clusters.

The thermal decomposition of free cationic iron-sulfur clusters FexSy+ (x = 0-7, y = 0-9) is investigated by collisional post-heating in the temperature range between 300 and 1000 K. With increasing temperature the preferential formation of stoichiometric FexSy+ (y = x) or near stoichiometric FexSy+ (y = x ± 1) clusters is observed. In particular, Fe4S4+ represents the most abundant product up to 600 K, Fe3S3+ and Fe3S2+ are preferably formed between 600 K and 800 K, and Fe2S2+ clearly dominates the cluster distribution above 800 K. These temperature dependent fragment distributions suggest a sequential fragmentation mechanism, which involves the loss of sulfur and iron atoms as well as FeS units, and indicate the particular stability of Fe2S2+. The potential fragmentation pathways are discussed based on first principles calculations and a mechanism involving the isomerization of the cluster prior to fragmentation is proposed. The fragmentation behavior of the iron-sulfur clusters is in marked contrast to the previously reported thermal dissociation of analogous iron-oxide clusters, which resulted in the release of O2 molecules only, without loss of metal atoms and without any tendency to form particular prominent and stable FexOy+ clusters at high temperatures.

Respiratory Motion Compensation for PET/CT with Motion Information Derived from Matched Attenuation-Corrected Gated PET Data.

Respiratory motion degrades the detection and quantification capabilities of PET/CT imaging. Moreover, mismatch between a fast helical CT image and a time-averaged PET image due to respiratory motion results in additional attenuation correction artifacts and inaccurate localization. Current motion compensation approaches typically have 3 limitations: the mismatch among respiration-gated PET images and the CT attenuation correction (CTAC) map can introduce artifacts in the gated PET reconstructions that can subsequently affect the accuracy of the motion estimation; sinogram-based correction approaches do not correct for intragate motion due to intracycle and intercycle breathing variations; and the mismatch between the PET motion compensation reference gate and the CT image can cause an additional CT-mismatch artifact. In this study, we established a motion correction framework to address these limitations. Methods: In the proposed framework, the combined emission-transmission reconstruction algorithm was used for phase-matched gated PET reconstructions to facilitate the motion model building. An event-by-event nonrigid respiratory motion compensation method with correlations between internal organ motion and external respiratory signals was used to correct both intracycle and intercycle breathing variations. The PET reference gate was automatically determined by a newly proposed CT-matching algorithm. We applied the new framework to 13 human datasets with 3 different radiotracers and 323 lesions and compared its performance with CTAC and non-attenuation correction (NAC) approaches. Validation using 4-dimensional CT was performed for one lung cancer dataset. Results: For the 10 18F-FDG studies, the proposed method outperformed (P < 0.006) both the CTAC and the NAC methods in terms of region-of-interest-based SUVmean, SUVmax, and SUV ratio improvements over no motion correction (SUVmean: 19.9% vs. 14.0% vs. 13.2%; SUVmax: 15.5% vs. 10.8% vs. 10.6%; SUV ratio: 24.1% vs. 17.6% vs. 16.2%, for the proposed, CTAC, and NAC methods, respectively). The proposed method increased SUV ratios over no motion correction for 94.4% of lesions, compared with 84.8% and 86.4% using the CTAC and NAC methods, respectively. For the 2 18F-fluoropropyl-(+)-dihydrotetrabenazine studies, the proposed method reduced the CT-mismatch artifacts in the lower lung where the CTAC approach failed and maintained the quantification accuracy of bone marrow where the NAC approach failed. For the 18F-FMISO study, the proposed method outperformed both the CTAC and the NAC methods in terms of motion estimation accuracy at 2 lung lesion locations. Conclusion: The proposed PET/CT respiratory event-by-event motion-correction framework with motion information derived from matched attenuation-corrected PET data provides image quality superior to that of the CTAC and NAC methods for multiple tracers.

Natural Products from Social Amoebae.

Natural products are invaluable sources of structural diversity and complexity ideally suited for the development of therapeutic agents. The search for novel bioactive molecules has prompted scientists to explore various ecological niches. Microorganisms have been shown to constitute such an important source. Despite their biosynthetic potential, social amoebae, that is, microorganisms with both a uni- and multicellular lifestyle, are underexplored regarding their secreted secondary metabolome. In this review, we present the structural diversity of amoebal natural products and discuss their biological functions as well as their total syntheses.