The dimensionality of infection networks among viruses infecting microbial eukaryotes and bacteria.

Diverse viruses and their hosts are interconnected through complex networks of infection, which are thought to influence ecological and evolutionary processes, but the principles underlying infection network structure are not well understood. Here we focus on network dimensionality and how it varies across 37 networks of viruses infecting eukaryotic phytoplankton and bacteria. We find that dimensionality is often strikingly low, with most networks being one- or two-dimensional, although dimensionality increases with network richness, suggesting that the true dimensionality of natural systems is higher. Low-dimensional networks generally exhibit a mixture of host partitioning among viruses and nestededness of host ranges. Networks of bacteria-infecting and eukaryote-infecting viruses possess comparable distributions of dimensionality and prevalence of nestedness, indicating that fundamentals of network structure are similar among domains of life and different viral lineages. The relative simplicity of many infection networks suggests that coevolutionary dynamics are often driven by a modest number of underlying mechanisms.

Remotely Bonded Bridging Dioxygen Ligands Enhance Hydrogen Transfer in a Silica-Supported Tetrairidium Cluster Catalyst.

A longstanding challenge in catalysis by noble metals has been to understand the origin of enhancements of rates of hydrogen transfer that result from the bonding of oxygen near metal sites. We investigated structurally well-defined catalysts consisting of supported tetrairidium carbonyl clusters with single-atom (apical iridium) catalytic sites for ethylene hydrogenation. Reaction of the clusters with ethylene and H2 followed by O2 led to the onset of catalytic activity as a terminal CO ligand at each apical Ir atom was removed and bridging dioxygen ligands replaced CO ligands at neighboring (basal-plane) sites. The presence of the dioxygen ligands caused a 6-fold increase in the catalytic reaction rate, which is explained by the electron-withdrawing capability induced by the bridging dioxygen ligands, consistent with the inference that reductive elimination is rate-determining. Electronic-structure calculations demonstrate an additional role of the dioxygen ligands, changing the mechanism of hydrogen transfer from one involving equatorial hydride ligands to that involving bridging hydride ligands. This mechanism is made evident by an inverse kinetic isotope effect observed in ethylene hydrogenation reactions with H2 and, alternatively, with D2 on the cluster incorporating the dioxygen ligands and is a consequence of quasi-equilibrated hydrogen transfer in this catalyst. The same mechanism accounts for rate enhancements induced by the bridging dioxygen ligands for the catalytic reaction of H2 with D2 to give HD. We posit that the mechanism involving bridging hydride ligands facilitated by oxygen ligands remote from the catalytic site may have some generality in catalysis by oxide-supported noble metals.

Transient, context-dependent fitness costs accompanying viral resistance in isolates of the marine microalga Micromonas sp. (class Mamiellophyceae).

Marine microbes are important in biogeochemical cycling, but the nature and magnitude of their contributions are influenced by their associated viruses. In the presence of a lytic virus, cells that have evolved resistance to infection have an obvious fitness advantage over relatives that remain susceptible. However, susceptible cells remain extant in the wild, implying that the evolution of a fitness advantage in one dimension (virus resistance) must be accompanied by a fitness cost in another dimension. Identifying costs of resistance is challenging because fitness is context-dependent. We examined the context dependence of fitness costs in isolates of the picophytoplankton genus Micromonas and their co-occurring dsDNA viruses using experimental evolution. After generating 88 resistant lineages from two ancestral Micromonas strains, each challenged with one of four distinct viral strains, we found resistance led to a 46% decrease in mean growth rate under high irradiance and a 19% decrease under low. After a year in culture, the experimentally selected lines remained resistant, but fitness costs had attenuated. Our results suggest that the cost of resistance in Micromonas is dependent on environmental conditions and the duration of population adaptation, illustrating the dynamic nature of fitness costs of viral resistance among marine protists.

Phosphine versus Carbene Metal Interactions: Bond Energies.

A variety of different ground-state structures of carbene and phosphine groups 1 and 2 cationic, group 11 cationic, and group 10 neutral complexes were studied using density functional theory (DFT) and correlated molecular orbital theory (CCSD(T)) methods. Geometries of complexes with phosphines were studied and compared to available experimental data. Among the three analyzed phosphine ligands, PH3, PMe3, and PPh3, PH3 was found to have noticeably smaller ligand binding energies (LBEs, ΔH298 K). PPh3 has the greatest LBEs with group 2 dications. The difference in LBEs for PMe3 and PPh3 in complexes with group 1 monocations and transition-metal (TM) complexes was significantly less pronounced. The stability and reactivity of phosphine complexes were analyzed and compared with those of previously studied N-heterocyclic carbenes (NHC). PH3 has smaller LBEs compared to NHC carbenes. The lower LBEs correlate with the hardness for M(11)+ complexes and correlate with both the hardness and ionic radii for the M(1)+ and M(2)2+ complexes. The presence of additional PH3 substituents on the metal center makes the LBE smaller compared to their unsubstituted or less substituted analogs. The presence of NH3 in a structure causes a smaller effect on binding, and, except for carbene-PtNH3, an increase in LBE was observed. Composite-correlated molecular orbital theory (G3MP2) was used to predict the LBE of various Lewis acidic ligands with PH3 and NHCs to contrast their binding behavior. Binding either phosphine or carbene to metal diamine complexes caused ligand exchange and transfer of NH3 to an outer coordination sphere.

Trophic strategies explain the ocean niches of small eukaryotic phytoplankton.

A large fraction of marine primary production is performed by diverse small protists, and many of these phytoplankton are phagotrophic mixotrophs that vary widely in their capacity to consume bacterial prey. Prior analyses suggest that mixotrophic protists as a group vary in importance across ocean environments, but the mechanisms leading to broad functional diversity among mixotrophs, and the biogeochemical consequences of this, are less clear. Here we use isolates from seven major taxa to demonstrate a tradeoff between phototrophic performance (growth in the absence of prey) and phagotrophic performance (clearance rate when consuming Prochlorococcus). We then show that trophic strategy along the autotrophy-mixotrophy spectrum correlates strongly with global niche differences, across depths and across gradients of stratification and chlorophyll a. A model of competition shows that community shifts can be explained by greater fitness of faster-grazing mixotrophs when nutrients are scarce and light is plentiful. Our results illustrate how basic physiological constraints and principles of resource competition can organize complexity in the surface ocean ecosystem.

NHC Carbene-Metal Complex Ligand Binding Energies.

The ligand binding energies (LBEs) of N-heterocyclic carbenes (NHCs) and CH2 and CF2 adducts with group 1, 2, 10, and 11 metals and complexes with metals from these groups are predicted at the coupled cluster CCSD(T) level of theory by using density functional theory optimized geometries. The differences in LBEs as a function of the metal and the types of bonding interactions as well as the type of carbene are described. The bonding between the alkali cations and alkaline earth dications is predominantly ionic with a linear correlation between the LBEs and the cation hardness. In contrast, the bonding behaviors of the group 10 and 11 metals and metal complexes have only a weak, indirect correlation between the LBEs and the metal hardness. The difference in bonding behavior between the groups of metals arises due to the accessibility of electron donation between the ligand and the metal in the transition metal complexes, which results in more covalent-like bonding behavior. The presence of the methyl groups on the NHC nitrogen results in only slightly more delocalized charge from the metal onto the ring, but there is significant redistribution of the charge on the ring. Saturation of the NHC ring had a much smaller effect on how the charge was distributed on the ring. The analysis of the bonding behavior of NHCs with various metal groups enables improved understanding of carbene-metal interactions to inform rational design of NHC-based systems.

Bond Dissociation Energies of Carbene-Carbene and Carbene-Main Group Adducts.

A range of carbene structures and their adducts with one another and with a selection of small-molecule electrophiles and nucleophiles were examined at the composite correlated molecular orbital theory G3MP2 level to explore ground-state "carbenic" structures, their stabilities, and reactivities. Differences between carbene general classification as a singlet electrophilic carbene or singlet nucleophilic carbene and their given reactivity are discussed. A key quantity is the carbon-carbon bond dissociation energy for carbene dimers or the carbene-adduct dissociation energy for other species. The carbene dimer bond dissociation energies span a wide range from 10 to 170 kcal/mol. The hydrogenation energies and singlet-triplet splitting were found to correlate best with the carbene's self-dimerization energy, whereas other descriptors do not. The proton and fluoride affinities of the carbenes alone prove inadequate for classifying reactivity among classes of carbenes. The self-dimerization bond dissociation energy, hydrogenation energy, and singlet-triplet splitting of various carbenes, despite sometimes large differences in proton affinity and other indicators of reactivity, provide usable metrics to correlate substantial amounts of thermodynamic and kinetic (reactivity) information regarding these structures.

Computational Predictions of the Hydrolysis of 2,4,6-Trinitrotoluene (TNT) and 2,4-Dinitroanisole (DNAN).

Hydrolysis is a common transformation reaction that can affect the environmental fate of many organic compounds. In this study, three proposed mechanisms of alkaline hydrolysis of 2,4,6-trinitrotoluene (TNT) and 2,4-dinitroaniline (DNAN) were investigated with plane-wave density functional theory (DFT) combined with ab initio and classical molecular dynamics (AIMD/MM) free energy simulations, Gaussian basis set DFT calculations, and correlated molecular orbital theory calculations. Most of the computations in this study were carried out using the Arrows web-based tools. For each mechanism, Meisenheimer complex formation, nucleophilic aromatic substitution, and proton abstraction reaction energies and activation barriers were calculated for the reaction at each relevant site. For TNT, it was found that the most kinetically favorable first hydrolysis steps involve Meisenheimer complex formation by attachment of OH- at the C1 and C3 arene carbons and proton abstraction from the methyl group. The nucleophilic aromatic substitution reactions at the C2 and C4 arene carbons were found to be thermodynamically favorable. However, the calculated activation barriers were slightly lower than in previous studies, but still found to be ΔG‡ ≈ 18 kcal/mol using PBE0 AIMD/MM free energy simulations, suggesting that the reactions are not kinetically significant. For DNAN, the barriers of nucleophilic aromatic substitution were even greater (ΔG‡ > 29 kcal/mol PBE0 AIMD/MM). The most favorable hydrolysis reaction for DNAN was found to be a two-step process in which the hydroxyl first attacks the C1 carbon to form a Meisenheimer complex at the C1 arene carbon C1-(OCH3)OH-, and subsequently, the methoxy anion (-OCH3) at the C1 arene carbon dissociates and the proton shuttles from the C1-OH to the dissociated methoxy group, resulting in methanol and an aryloxy anion.

Mixotrophy in nanoflagellates across environmental gradients in the ocean.

Mixotrophy, the combination of autotrophic and heterotrophic nutrition, is a common trophic strategy among unicellular eukaryotes in the ocean. There are a number of hypotheses about the conditions that select for mixotrophy, and field studies have documented the prevalence of mixotrophy in a range of environments. However, there is currently little evidence for how mixotrophy varies across environmental gradients, and whether empirical patterns support theoretical predictions. Here I synthesize experiments that have quantified the abundance of phototrophic, mixotrophic, and heterotrophic nanoflagellates, to ask whether there are broad patterns in the prevalence of mixotrophy (relative to pure autotrophy and heterotrophy), and to ask whether observed patterns are consistent with a trait-based model of trophic strategies. The data suggest that mixotrophs increase in abundance at lower latitudes, while autotrophs and heterotrophs do not, and that this may be driven by increased light availability. Both mixotrophs and autotrophs increase greatly in productive coastal environments, while heterotrophs increase only slightly. These patterns are consistent with a model of resource competition in which nutrients and carbon can both limit growth and mixotrophs experience a trade-off in allocating biomass to phagotrophy vs. autotrophic functions. Importantly, mixotrophy is selected for under a range of conditions even when mixotrophs experience a penalty for using a generalist trophic strategy, due to the synergy between photosynthetically derived carbon and prey-derived nutrients. For this reason mixotrophy is favored relative to specialist strategies by increased irradiance, while at the same time increased nutrient supply increases the competitive ability of mixotrophs against heterotrophs.

Fluoro-nitrogen Cations.

The crystal structures of [NH3 F]+ [CF3 SO3 ]- , [NH2 F2 ]+ [SbF6 ]- , and [N2 F3 ]+ [Sb3 F16 ]- have been determined, representing the first structural characterizations of these simple fluoro-nitrogen cations. The influences of the hybridization of the central nitrogen atom and of the number of fluorine substituents on the N-F bond lengths are evaluated for the series N2 F+ , N2 F3 + , NF2 O+ , NH3 F+ , NH2 F2 + , and NF4 + . It is shown that the N-F bond length decreases from 1.40 Što 1.26 Šwith increasing fluorine substitution and increasing s-character of the nitrogen atom, and that unusual N-F bond lengths reported in the previous literature are caused by disorder problems.

Making sense of virus size and the tradeoffs shaping viral fitness.

Viruses span an impressive size range, with genome length varying a thousandfold and virion volume nearly a millionfold. For cellular organisms the scaling of traits with size is a pervasive influence on ecological processes, but whether size plays a central role in viral ecology is unknown. Here, we focus on viruses of aquatic unicellular organisms, which exhibit the greatest known range of virus size. We outline hypotheses within a quantitative framework, and analyse data where available, to consider how size affects the primary components of viral fitness. We argue that larger viruses have fewer offspring per infection and slower contact rates with host cells, but a larger genome tends to increase infection efficiency, broaden host range, and potentially increase attachment success and decrease decay rate. These countervailing selective pressures may explain why a breadth of sizes exist and even coexist when infecting the same host populations. Oligotrophic ecosystems may be enriched in "giant" viruses, because environments with resource-limited phagotrophs at low concentrations may select for broader host range, better control of host metabolism, lower decay rate and a physical size that mimics bacterial prey. Finally, we describe where further research is needed to understand the ecology and evolution of viral size diversity.

Electron paramagnetic spectrum of dimanganic human serum transferrin.

An EPR signal for Mn(III) bound to the metal transport protein transferrin has been detected for the first time. The temperature dependence and simulations of the EPR signal are consistent with the Mn(III) centers being six-coordinate in an elongated tetragonal environment. Thus, the incorporation of Mn(III) within the Tf active site does not vastly alter the coordination number or active site geometry relative to native Fe(III)2-Tf. This parallel mode EPR signal for Mn(III)2-Tf could prove valuable for future studies aimed at determining the physiological relevance of Mn(III)2-Tf.

Glitazone loaded fat enhances adiponectin production and inhibits breast cancer cell proliferation.

Obesity and diabetes are both associated risk factors for developing breast cancer and poor patient outcomes. Adipose cells are an important endocrine system and are the main producer of adiponectin, with lean patients having higher circulating levels. Patients with diabetes are often treated with thiazolidinediones, glitazones, which also increase adiponectin production. Importantly high circulating levels of adiponectin and treatment with glitazone are associated with increased breast cancer patient survival. This study investigates the potential of using adipose tissue laden with glitazones to act as a drug depot, increase adiponectin levels, and locally release glitazones to inhibit breast cancer cell proliferation. The breast cancer cell lines MCF-7 and MBA-MD-231, and the normal breast epithelial cell line MCF-10A were exposed to media containing a range of concentrations of recombinant adiponectin, pioglitazone, or conditioned media obtained from pioglitazone laden adipose tissue to determine the impact of the different treatments on cell proliferation. The MCF-7 cells demonstrated the greatest reduction in proliferation upon exposure to adiponectin and pioglitazone with lower reductions observed in the MDA-MD-231 and MCF-10a cell lines. All three cell lines exhibited reductions in proliferation in the presence of pioglitazone loaded adipose tissue. Additionally, adiponectin and pioglitazone levels were higher in the media from glitazone loaded adipose tissue. Drug loaded adipose tissue could potentially be used to deliver adiponectin and glitazone to breast cancer cells and inhibit proliferation. Future research will examine the potential efficacy of this treatment approach in vivo.

Evolutionarily stable communities: a framework for understanding the role of trait evolution in the maintenance of diversity.

Biological diversity depends on the interplay between evolutionary diversification and ecological mechanisms allowing species to coexist. Current research increasingly integrates ecology and evolution over a range of timescales, but our common conceptual framework for understanding species coexistence requires better incorporation of evolutionary processes. Here, we focus on the idea of evolutionarily stable communities (ESCs), which are theoretical endpoints of evolution in a community context. We use ESCs as a unifying framework to highlight some important but under-appreciated theoretical results, and we review empirical research relevant to these theoretical predictions. We explain how, in addition to generating diversity, evolution can also limit diversity by reducing the effectiveness of coexistence mechanisms. The coevolving traits of competing species may either diverge or converge, depending on whether the number of species in the community is low (undersaturated) or high (oversaturated) relative to the ESC. Competition in oversaturated communities can lead to extinction or neutrally coexisting, ecologically equivalent species. It is critical to consider trait evolution when investigating fundamental ecological questions like the strength of different coexistence mechanisms, the feasibility of ecologically equivalent species, and the interpretation of different patterns of trait dispersion.

Host Traits Drive Viral Life Histories across Phytoplankton Viruses.

Viruses are integral to ecological and evolutionary processes, but we have a poor understanding of what drives variation in key traits across diverse viruses. For lytic viruses, burst size, latent period, and genome size are primary characteristics controlling host-virus dynamics. Here we synthesize data on these traits for 75 strains of phytoplankton viruses, which play an important role in global biogeochemistry. We find that primary traits of the host (genome size, growth rate) explain 40%-50% of variation in burst size and latent period. Specifically, burst size and latent period both exhibit saturating relationships versus the host∶virus genome size ratio, with both traits increasing at low genome size ratios while showing no relationship at high size ratios. In addition, latent period declines as host growth rate increases. We analyze a model of latent period evolution to explore mechanisms that could cause these patterns. The model predicts that burst size may often be set by the host genomic resources available for viral construction, while latent period evolves to permit this maximal burst size, modulated by host metabolic rate. These results suggest that general mechanisms may underlie the evolution of diverse viruses. Future extensions of this work could help explain viral regulation of host populations, viral influence on community structure and diversity, and viral roles in biogeochemical cycles.

Operative Time and Flap Failure in Unilateral and Bilateral Free Flap Breast Reconstruction.

BACKGROUND: There is an increasing trend toward bilateral breast reconstruction. Using the National Surgical Quality Improvement Program (NSQIP) database, we sought to understand the association between unilateral and bilateral free flap breast reconstruction and operative time and flap failure. METHODS: We selected a cohort of patients undergoing free flap breast reconstruction using the 2005 to 2010 NSQIP database. Cases were divided into unilateral and bilateral reconstruction. Subgroup analyses were performed dividing cases into delayed and immediate reconstruction. The effect of patient characteristics including age, body mass index (BMI), history of diabetes, and the American Society of Anesthesiologists' classification on operative time and flap failure was examined using univariable and multivariable regression models. Rates and odds ratios (OR) were reported using the multivariable gamma and logistic regression models, respectively. RESULTS: There were 691 free flap breast reconstructions performed in the cohort and 29.1% were bilateral cases. There was a 78-minute increase in the median operative time when comparing unilateral and bilateral reconstruction (p = 0.005). Patients undergoing bilateral reconstructions were generally younger and had fewer comorbidities compared with unilateral reconstructions. There was no significant association between bilateral reconstruction and flap failure. Immediate bilateral reconstructions had a significant increase in median operative time compared with immediate unilateral reconstructions (563 versus 480 minutes, p = 0.002) but no significant increase in operative time was noted when comparing delayed unilateral and delayed bilateral reconstructions. Prolonged operative time was associated with flap failure after adjusting for age and BMI (OR 1.17, p < 0.001). CONCLUSIONS: Bilateral free flap breast reconstruction can be performed safely despite an increase in operative time when compared with unilateral reconstruction.

Community trait structure in phytoplankton: seasonal dynamics from a method for sparse trait data.

The distribution of functional traits in communities, and how trait distributions shift over time and space, is critical information for understanding community structure, the maintenance of diversity, and community effects on ecosystem function. It is often the case that traits tightly linked to ecological performance, such as physiological capacities, are laborious to measure and largely unknown for speciose communities; however, these traits are particularly important for unraveling the mechanistic basis of community structure. Here I develop a method combining sparse trait data with a statistical niche model to infer trait distributions for phytoplankton communities and how they vary over 10 yr in the western English Channel. I find that community-average nitrate affinity, light-limited growth rate, and maximum growth rate all show major seasonal patterns, reflecting alternate limitation by light vs. nitrogen. Trait diversity exhibits a variety of patterns distinct from community trait means, which suggests complex regulation of functional diversity. Patterns such as these are important for predicting how ocean ecosystems will respond to global change, and for developing trait-based models of emergent community structure. The statistical approach used here could be applied to any kind of organism, if it exhibits strong relationships between traits and statistical niche estimates.

Volatile communication between plants that affects herbivory: a meta-analysis.

Volatile communication between plants causing enhanced defence has been controversial. Early studies were not replicated, and influential reviews questioned the validity of the phenomenon. We collected 48 well-replicated studies and found overall support for the hypothesis that resistance increased for individuals with damaged neighbours. Laboratory or greenhouse studies and those conducted on agricultural crops showed stronger induced resistance than field studies on undomesticated species, presumably because other variation had been reduced. A cumulative analysis revealed that early, non-replicated studies were more variable and showed less evidence for communication. Effects of habitat and plant growth form were undetectable. In most cases, the mechanisms of resistance and alternative hypotheses were not considered. There was no indication that some response variables were more likely to produce large effects. These results indicate that plants of diverse taxonomic affinities and ecological conditions become more resistant to herbivores when exposed to volatiles from damaged neighbours.

Disparities in Electronic Cigarette Use: A Narrative Review.

The prevalence of electronic cigarette use has been declared an epidemic by the U.S. Surgeon General in 2018, particularly among youth aged 18-24 years old. Little is known about the differential use of e-cigarettes by different groups. PubMed, Cochrane, and Google Scholar were used to find relevant articles. A total of 77 articles were included. The extant literature reveals disparities in e-cigarette use by race/ethnicity and sexuality/gender. There are conflicting conclusions regarding disparities by socioeconomic status.

Social Determinants of Health, Risk and Resilience against Alzheimer's Disease and Related Dementias: The Healthy Brain Initiative.

Background: Few studies have investigated associations between perceived social determinants of health (SDOH) and Alzheimer's disease and related dementia (ADRD) biomarkers or between SDOH and resilience against ADRD. Objective: To examine associations between perceived and objective SDOH and ADRD-related outcomes. Methods: We used cross-sectional data on≥50-year-olds without dementia in the Healthy Brain Initiative (n = 162). Questionnaires captured trust in neighbors and indices of perceived neighborhood greenspace access, time spent in neighborhood greenspaces, and interpersonal discrimination. Residential addresses were linked to 2021 Area Deprivation Index scores. The Vulnerability Index (VI) is based on 12 dementia risk factors (e.g., age, race/ethnicity, diabetes) and Resilience Index (RI) is based on 6 protective factors (e.g., diet, mindfulness, physical activity). Cognitive measured included number symbol coding task and Montreal Cognitive Assessment. Biomarkers included Aß42/40 and pTau-217/npTau-217, hippocampal and white matter hyperintensity volume, lipoprotein A, and high-sensitivity c-reactive protein. Results: Perceived greater access to greenspaces (estimate = 2.83, 95% CI = 1.40-4.26) and greater time in neighborhood greenspaces were associated with greater RI scores (estimate = 2.30, 95% CI = 1.24-3.35). Reporting greater discrimination (estimate = 0.10, 95% CI = 0.04-0.16) and living in higher deprivation neighborhoods were associated with greater VI scores (estimate = 0.017, 95% CI = 0.003-0.032). Greater discrimination was associated with greater white matter hyperintensity volume (estimate = 0.27, 95% CI = 0.04-0.51). Conclusions: Perceived greenspace access and time spent in greenspaces were associated with resilience against ADRD, and interpersonal discrimination was associated with vulnerability to ADRD. Future work needs to validate perceived SDOH measures, examine associations in racially/ethnic diverse populations, and investigate longitudinal associations between SDOH and ADRD-related biomarkers.