Evolutionary genomics of socially polymorphic populations of Pogonomyrmex californicus.

BACKGROUND: Social insects vary considerably in their social organization both between and within species. In the California harvester ant, Pogonomyrmex californicus (Buckley 1867), colonies are commonly founded and headed by a single queen (haplometrosis, primary monogyny). However, in some populations in California (USA), unrelated queens cooperate not only during founding (pleometrosis) but also throughout the life of the colony (primary polygyny). The genetic architecture and evolutionary dynamics of this complex social niche polymorphism (haplometrosis vs pleometrosis) have remained unknown. RESULTS: We provide a first analysis of its genomic basis and evolutionary history using population genomics comparing individuals from a haplometrotic population to those from a pleometrotic population. We discovered a recently evolved (< 200 k years), 8-Mb non-recombining region segregating with the observed social niche polymorphism. This region shares several characteristics with supergenes underlying social polymorphisms in other socially polymorphic ant species. However, we also find remarkable differences from previously described social supergenes. Particularly, four additional genomic regions not in linkage with the supergene show signatures of a selective sweep in the pleometrotic population. Within these regions, we find for example genes crucial for epigenetic regulation via histone modification (chameau) and DNA methylation (Dnmt1). CONCLUSIONS: Altogether, our results suggest that social morph in this species is a polygenic trait involving a potential young supergene. Further studies targeting haplo- and pleometrotic individuals from a single population are however required to conclusively resolve whether these genetic differences underlie the alternative social phenotypes or have emerged through genetic drift.

(3+2)-Cycloadditions of Levoglucosenone (LGO) with Fluorinated Nitrile Imines Derived from Trifluoroacetonitrile: An Experimental and Computational Study.

The in situ-generated N-aryl nitrile imines derived from trifluoroacetonitrile smoothly undergo (3+2)-cycloadditions onto the enone fragment of the levoglucosenone molecule, yielding the corresponding, five-membered cycloadducts. In contrast to the 'classic' C(Ph),N(Ph) nitrile imine, reactions with fluorinated C(CF3),N(Ar) analogues lead to stable pyrazolines in a chemo- and stereoselective manner. Based on the result of X-ray single crystal diffraction analysis, their structures were established as exo-cycloadducts with the location of the N-Ar terminus of the 1,3-dipole at the α-position of the enone moiety. The DFT computation demonstrated that the observed reaction pathway results from the strong dominance of kinetic control over thermodynamic control.

Diastereoselective synthesis and structure-affinity relationships of σ1 receptor ligands with spirocyclic scaffold.

Spirocyclic scaffolds play an increasing role in drug discovery as they define a rigid three-dimensional space to increase specific interactions with protein binding sites. Herein, a spirocyclic center was introduced into the lead compound 1 to rigidify its flexible benzylaminoethyl side chain. The key step of the synthesis was the reaction of different α,ß-unsaturated amides 6 and 13-16 with methyl acrylate in the presence of TBDMSOTf. DFT calculations explain the mechanism of this transformation as concerted Diels-Alder reaction (functionals B3LYP and TPSS) or double (aza)-Michael addition (functionals PBE and wB97X-D). After separation of the diastereomeric spirocyclic products 8 and 17-20, LiAlH4 reduction provided the spirocyclic hydroxymethyl piperidines 21a,b-25a,b showing low nanomolar σ1 affinity (Ki < 100 nM). trans-Configured ligands (a-series) showed higher or equal σ1 affinity and higher selectivity over σ2 receptors and GluN2B-NMDA receptors than their cis-configured analogs (b-series). The additional hydroxymethyl moiety brings the log D7.4 value in a promising range. The high σ1 affinity (Ki = 3.6 nM) and the low lipophilicity result in the highest lipophilic ligand efficiency for the dispiro compound 23a (LLE = 6.0). The spirocyclic compounds reported herein and in particular the dispiro compound 23a demonstrate that ligands containing a large number of sp3 C-atoms possess favorable pharmacological (σ1 receptor affinity, receptor selectivity) and physicochemical properties (log D7.4 value) resulting in promising LLE.

The Boekelheide Rearrangement of Pyrimidine N-oxides as a Case Study of Closed or Open Shell Reactions - Experimental and Computational Evidence for the Participation of Radical Intermediates.

In a case study, the acetic anhydride-promoted reaction of a model pyrimidine N-oxide to the corresponding 4-acetoxymethyl-substituted pyrimidine derivative (Boekelheide rearrangement) was investigated in detail by experiment and quantum chemical calculations. The reaction conditions were varied and several side products formed in low to moderate yields were identified. These experiments indicate that a (pyrimidin-4-yl)methyl radical is one of the key species of the rearrangement. This interpretation was supported by the fact that rearrangements performed in solvents which can easily lose hydrogen atoms, afford considerable quantities of products incorporating the solvent. With TEMPO the key radical could be trapped. Other carboxylic acid anhydrides confirm the conclusion that the Boekelheide rearrangement of the model pyrimidine N-oxide proceeds, at least in part, via radical intermediates. The high level closed and open shell quantum chemical calculations show that concerted [3,3]-sigmatropic rearrangements or stepwise processes, either via ion pairs or via radicals, are energetically feasible.

Semisynthetic Approach toward Biologically Active Derivatives of Phenylspirodrimanes from S. chartarum.

The phenylspirodrimanes (PSDs) from Stachybotrys chartarum represent a structurally diverse group of meroterpenoids, which, on the one hand, exhibit a structural exclusivity since their occurrence is not known for any other species and, on the other hand, offer access to chemically and biologically active compounds. In this study, phenylspirodrimanes 1-3 were isolated from S. chartarum and their water-mediated Cannizzaro-type transformation was investigated using quantum chemical DFT calculations substantiated by LC-MS and NMR experiments. Considering the inhibitory activity of PSDs against proteolytic enzymes and their modulatory effect on plasminogen, PSDs 1-3 were used as a starting material for the synthesis of their corresponding biologically active lactams. To access the library of the PSD derivatives and screen them against physiologically relevant serine proteases, a microscale semisynthetic approach was developed. This allowed us to generate the library of 35 lactams, some of which showed the inhibitory activity against physiologically relevant serine proteases such as thrombin, FXIIa, FXa, and trypsin. Among them, the agmatine-derived lactam 16 showed the highest inhibitory activity against plasma coagulation factors and demonstrated the anticoagulant activity in two plasma coagulation tests. The semisynthetic lactams were significantly less toxic compared to their parental natural PSDs.

How Individualized Niches Arise: Defining Mechanisms of Niche Construction, Niche Choice, and Niche Conformance.

Organisms interact with their environments in various ways. We present a conceptual framework that distinguishes three mechanisms of organism-environment interaction. We call these NC3 mechanisms: niche construction, in which individuals make changes to the environment; niche choice, in which individuals select an environment; and niche conformance, in which individuals adjust their phenotypes in response to the environment. Each of these individual-level mechanisms affects an individual's phenotype-environment match, its fitness, and its individualized niche, defined in terms of the environmental conditions under which the individual can survive and reproduce. Our framework identifies how individuals alter the selective regimes that they and other organisms experience. It also places clear emphasis on individual differences and construes niche construction and other processes as evolved mechanisms. The NC3 mechanism framework therefore helps to integrate population-level and individual-level research.

Digest: Better constructing the future than choosing a new habitat.

What strategy should an individual follow in a heterogeneous environment when its phenotype is not optimized for its current environment: make changes to the environment (habitat construction), move to a different place (habitat choice), or both? Scheiner et al. used an individual-based model to investigate the interaction of habitat choice and habitat construction. In most situations, habitat construction was superior to either habitat selection or a mixed strategy.

Insights into Ergochromes of the Plant Pathogen Claviceps purpurea.

Claviceps purpurea is an ergot fungus known for its neurotropic alkaloids, which have been identified as the main cause of ergotism, a livestock and human disease triggered by ergot consumption. Tetrahydroxanthone dimers, the so-called ergopigments, presumably also contribute to this toxic effect. Overexpression of the cluster-specific transcription factor responsible for the formation of these pigments in C. purpurea led to the isolation of three new metabolites (8-10). The new pigments were characterized utilizing HRMS, NMR techniques, and CD spectroscopy and shown to be xanthone dimers. Secalonic acid A and its 2,4'- and 4,4'-linked isomers were also isolated, and their absolute configuration was investigated. The contribution of secalonic acid A, its isomers, and new metabolites to the toxicity of C. purpurea was investigated in HepG2 and CCF-STTG1 cells. Along with cytotoxic properties, secalonic acid A was found to inhibit topoisomerase I and II activity.

Digest: Changing environment often easier than changing phenotype.

What strategy should an individual follow when faced with a suboptimal environment: change the environment, adapt to the environment, or both? Scheiner et al. used an individual-based model to address the interaction of plasticity and habitat construction with different life histories in a heterogeneous environment. In most situations, habitat construction was superior to either plasticity or a mixed strategy, but not always, and specific conditions may favor plasticity.

Hetero-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies.

The hetero-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2H-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27-2.58 Å) and longer N..C-distances (3.02-3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4-tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C‒S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies.

Genome assembly and annotation of the California harvester ant Pogonomyrmex californicus.

The harvester ant genus Pogonomyrmex is endemic to arid and semiarid habitats and deserts of North and South America. The California harvester ant Pogonomyrmex californicus is the most widely distributed Pogonomyrmex species in North America. Pogonomyrmex californicus colonies are usually monogynous, i.e. a colony has one queen. However, in a few populations in California, primary polygyny evolved, i.e. several queens cooperate in colony founding after their mating flights and continue to coexist in mature colonies. Here, we present a genome assembly and annotation of P. californicus. The size of the assembly is 241 Mb, which is in agreement with the previously estimated genome size. We were able to annotate 17,889 genes in total, including 15,688 protein-coding ones with BUSCO (Benchmarking Universal Single-Copy Orthologs) completeness at a 95% level. The presented P. californicus genome assembly will pave the way for investigations of the genomic underpinnings of social polymorphism in the number of queens, regulation of aggression, and the evolution of adaptations to dry habitats.

Synthesis of Alkyl Silanes via Reaction of Unactivated Alkyl Chlorides and Triflates with Silyl Lithium Reagents.

The reaction of unactivated secondary and primary alkyl chlorides as well as primary alkyl triflates with silyl lithium reagents to access tetraorganosilanes is reported. These nucleophilic substitutions proceed in the absence of any transition metal catalyst under mild conditions in moderate to very good yields. The silyl lithium reagents are readily generated from the corresponding commercially available chlorosilanes. Enantioenriched secondary alkyl chlorides react with high stereospecificity under inversion of configuration.

New Reactivity Patterns in 3H-Phosphaallene Chemistry [Aryl-P=C=C(H)-tBu]: Hydroboration of the C=C Bond, Deprotonation and Trimerisation.

3H-Phosphaallenes, R-P=C=C(H)C-R' (3), are accessible in a multigram scale on a new and facile route and show a fascinating chemical reactivity. BH3 (SMe2 ) and 3 a (R=Mes*, R'=tBu) afforded by hydroboration of the C=C bonds of two phosphaallene molecules an unprecedented borane (7) with the B atom bound to two P=C double bonds. This compound represents a new FLP based on a B and two P atoms. The increased Lewis acidity of the B atom led to a different reaction course upon treatment of 3 a with H2 B-C6 F5 (SMe2 ). Hydroboration of a C=C bond of a first phosphaallene is followed in a typical FLP reaction by the coordination of a second phosphaallene molecule via B-C and P-B bond formation to yield a BP2 C2 heterocycle (8). Its B-P bond is short and the B-bound P atom has a planar surrounding. Treatment of 3 a with tBuLi resulted in deprotonation of the ß-C atom of the phosphaallene (9). The Li atom is bound to the P atom as demonstrated by crystal structure determination, quantum chemical calculations and reactions with HCl, Cl-SiMe3 or Cl-PtBu2 . The thermally unstable phosphaallene Ph-P=C=C(H)-tBu gave a unique trimeric secondary product by P-P, P-C and C-C bond formation. It contains a P2 C4 heterocycle and was isolated as a W(CO)4 complex with two P atoms coordinated to W (15).

Biomimetic in vitro test system for evaluation of dental implant materials.

OBJECTIVES: Before application in dental practice, novel dental materials are tested in vitro and in vivo to ensure safety and functionality. However, transferability between preclinical and clinical results is often limited. To increase the predictive power of preclinical testing, a biomimetic in vitro test system that mimics the wound niche after implantation was developed. METHODS: First, predetermined implant materials were treated with human blood plasma, M2 macrophages and bone marrow stromal stem cells. Thereby, the three-dimensional wound niche was simulated. Samples were cultured for 28 days, and subsequently analyzed for metabolic activity and biomineralization. Second test level involved a cell-infiltrated bone substitute material for an osseointegration assay to measure mechanical bonding between dental material and bone. Standard and novel dental materials validated the developed test approach. RESULTS: The developed test system for dental implant materials allowed quantification of biomineralization on implant surface and assessment of the functional stability of mineralized biomaterial-tissue interface. Human blood plasma, M2 macrophages and bone marrow stromal stem cells proved to be crucial components for predictive assessment of implant materials in vitro. Biocompatibility was demonstrated for all tested materials, whereas the degree of deposited mineralized extracellular matrix and mechanical stability differed between the tested materials. Highest amount of functional biomineralization was determined to be on carbon-coated implant surface. SIGNIFICANCE: As an ethical alternative to animal testing, the established in vitro dental test system provides an economic and mid-throughput evaluation of novel dental implant materials or modifications thereof, by applying two successive readout levels: biomineralization and osseointegration.

Tridentate Ligand with Three Carbanions as Donor Atoms: Formation of Dinuclear, Heptacyclic Complexes of Boron, Aluminum, or Gallium with B-C-B, Al-C-Al, or Ga-C-Ga Three-Center-Two-Electron Bonds.

The trilithium compound 1,3-[PhMe2Si-C(Li)═C(H)]2C6H3Li (2b) reacted with BCl3, AlCl3, or GaCl3 by salt elimination to yield dinuclear heptacyclic compounds (4). Two tridentate tricarbanionic ligands coordinate two B, Al, or Ga atoms and adopt a helical arrangement of the ligands around a central E2 unit. The unusual structures comprise E2C2 heterocycles with two 3c-2e (three-center-two-electron) E-C-E bonds and two C atoms of aromatic rings in the bridging positions. While such a bonding situation is well-documented in Al chemistry, it is rare for B and Ga compounds. Insight into the bonding situation of the molecules is provided by DFT calculations.

Evaluation of model materials for CAD/CAM in vitro studies.

AIM: Evaluation of appropriate models for computer-aided design/computer-aided manufacturing (CAD/CAM) in vitro studies by investigation of different model materials regarding suitability for intraoral scanners and dimensional stability. MATERIALS AND METHODS: A typodont model was prepared to accommodate a 10-unit prosthesis. The model was duplicated using six different materials: class IV die stone (DS), cobalt-chrome molybdenum (CoCrMo), epoxy resin (EPOX), polyurethane (PU), titanium (TI), and zirconia (ZI). An intraoral scanner was used to obtain three scans of each model. Reference datasets were generated using micro-computed tomography (micro-CT). The first scan was compared with the corresponding reference micro-CT dataset to assess its trueness. The precision was measured by comparing all scans within one test group. For the evaluation of dimensional stability, micro-CT was used to generate three-dimensional (3D) datasets of the models at different time intervals over a 6-week period. The models were kept under constant conditions during the study. All datasets were analyzed with software that determined the deviation of two datasets by alignment using a best-fit algorithm. RESULTS: The criterion of trueness was fulfilled by CoCrMo, EPOX, PU, and the typodont model. Scans of CoCrMo and ZI showed the best precision. PU and the typodont model did not meet the requirement of dimensional stability, whereas EPOX and gypsum were stable only for a period of 10 days. CONCLUSION: The CoCrMo model was the only one that met all the criteria for an appropriate model for CAD/CAM in vitro studies. The other investigated materials either lacked dimensional stability or could not be scanned accurately and reproducibly.

Aspects of Phosphaallene Chemistry: Heat-Induced Formation of 1,2-Dihydrophosphetes by Intramolecular Nucleophilic Aromatic Substitution and Photochemical Generation of Tricyclic Phosphiranes.

3H-Phosphaallenes are accessible on a new and facile route and show a fascinating chemical behavior. The thermally induced rearrangement of Mes*P═C═C(H)R' (R' = tBu, Ad) afforded by C-H activation, isobutene elimination, and C-C and P-H bond formation bicyclic 1-benzo-dihydrophosphetes (2) with PC3 heterocycles. DFT calculations suggest a mechanism with intramolecular nucleophilic aromatic substitution and replacement of an alkyl group by the nucleophilic α-C atom of the phosphaallene. These bicycles formed W(CO)5 complexes (3) or afforded 1,2-dihydrophosphetes with P-bound alkenyl groups by catalyst-free hydrophosphination of alkynes (4 and 5). The resulting bulky phosphines formed complexes with IrCp*Cl2, RuCl2, AuCl, or CuO3SCF3. The Ru atom is coordinated by the P atom and a phenyl group. Irradiation of TripP═C═C(H)tBu led by the insertion of the central C atom of the P═C═C group into the α-C-H bond of an iPr substituent and by C-C and P-C bond formation to a new isomer of phosphaallenes, 10, which features a strained PC2 heterocycle. It formed adducts with M(CO)5 (M = Cr, Mo, W) and AuCl and reacted with SO2Cl2 by cleavage of one of the phosphirane P-C bonds to yield PC4 or PC5 heterocycles. Hydrolysis yielded a PC5 compound with a P(O)Cl group.

The [4+2]-Cycloaddition of α-Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero-Diels-Alder Reactions-Experimental and Computational Studies.

The [4+2]-cycloadditions of α-nitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styryl-substituted 4H-1,5,2-oxathiazines in moderate to good yields. Of the eight conceivable hetero-Diels-Alder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the α-nitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bis-heterocyclic [4+2]-cycloadducts. The experiments are supported by high-level DFT calculations that were also extended to related hetero-Diels-Alder reactions of other nitroso compounds and thioketones. These calculations reveal that the title cycloadditions are kinetically controlled processes confirming the role of thioketones as superdienophiles. The computational study was also applied to the experimentally studied thiochalcone dimerization, and showed that the 1,2-dithiin and 2H-thiopyran isomers are in equilibrium with the monomer. Again, the DFT calculations indicate kinetic control of this process.

Digest: Evolution of eusociality favored by split sex ratios under worker-control.

Eusociality has repeatedly independently evolved in ants, bees, and wasps (Hymenoptera), leading to the idea that haplodiploidy may be an important driving factor in this group. Using a modeling approach, Quiñones et al. show that split sex ratios and worker control of sex ratios (achieved by removal of male brood) can promote the initial evolution of helping raise offspring of related individuals. However, over time, these factors can result in social polymorphism, that is, a mix of solitary and social nests, or to eusocial colonies with three different strategies, namely those that produce mostly females, mostly males, or a balanced sex ratio.

Forty years of reform and opening up: China's progress toward a sustainable path.

After 40 years of reform and "opening up," China has made remarkable economic progress. Such economic prosperity, however, has been coupled with environmental degradation. We analyze diverse long-term data to determine whether China is experiencing a decoupling of economic growth and environmental impacts, and where China stands with respect to the Sustainable Development Goals (SDGs) in terms of reducing regional division, urban-rural gap, social inequality, and land-based impacts on oceans. The results highlight that China's desire to achieve "ecological civilization" has resulted in a decoupling trend for major pollutants since 2015, while strong coupling remains with CO2 emissions. Progress has been made in health care provision, poverty reduction, and gender equity in education, while income disparity continues between regions and with rural-urban populations. There is a considerable way to go toward achieving delivery of the SDGs; however, China's progress toward economic prosperity and concomitant sustainability provides important insights for other countries.