A Catalytic Reactor for the Organocatalyzed Enantioselective Continuous Flow Alkylation of Aldehydes

The use of immobilized metal-free catalysts offers the unique possibility to develop sustainable processes in flow mode. The challenging intermolecular organocatalyzed enantioselective alkylation of aldehydes was performed for the first time under continuous flow conditions. By using a packed-bed reactor filled with readily available supported enantiopure imidazolidinone, different aldehydes were treated with three distinct cationic electrophiles. In the organocatalyzed α-alkylation of aldehydes with 1,3-benzodithiolylium tetrafluoroborate, excellent enantioselectivities, in some cases even better than those obtained in the flask process (up to 95 % ee at 25 °C), and high productivity (more than 3800 h−1) were obtained, which thus shows that a catalytic reactor may continuously produce enantiomerically enriched compounds. Treatment of the alkylated products with Raney-nickel furnished enantiomerically enriched α-methyl derivatives, key intermediates for active pharmaceutical ingredients and natural products

Complete Plastome Sequences of Equisetum arvense and Isoetes flaccida: Implications for Phylogeny and Plastid Genome Evolution of Early Land Plant Lineages

Background Despite considerable progress in our understanding of land plant phylogeny, several nodes in the green tree of life remain poorly resolved. Furthermore, the bulk of currently available data come from only a subset of major land plant clades. Here we examine early land plant evolution using complete plastome sequences including two previously unexamined and phylogenetically critical lineages. To better understand the evolution of land plants and their plastomes, we examined aligned nucleotide sequences, indels, gene and nucleotide composition, inversions, and gene order at the boundaries of the inverted repeats. Results We present the plastome sequences of Equisetum arvense, a horsetail, and of Isoetes flaccida, a heterosporous lycophyte. Phylogenetic analysis of aligned nucleotides from 49 plastome genes from 43 taxa supported monophyly for the following clades: embryophytes (land plants), lycophytes, monilophytes (leptosporangiate ferns + Angiopteris evecta + Psilotum nudum + Equisetum arvense), and seed plants. Resolution among the four monilophyte lineages remained moderate, although nucleotide analyses suggested that P. nudum and E. arvense form a clade sister to A. evecta + leptosporangiate ferns. Results from phylogenetic analyses of nucleotides were consistent with the distribution of plastome gene rearrangements and with analysis of sequence gaps resulting from insertions and deletions (indels). We found one new indel and an inversion of a block of genes that unites the monilophytes. Conclusions Monophyly of monilophytes has been disputed on the basis of morphological and fossil evidence. In the context of a broad sampling of land plant data we find several new pieces of evidence for monilophyte monophyly. Results from this study demonstrate resolution among the four monilophytes lineages, albeit with moderate support; we posit a clade consisting of Equisetaceae and Psilotaceae that is sister to the true ferns, including Marattiaceae

Efficient 1400-1600 nm Circularly Polarized Luminescence from a Tuned Chiral Erbium Complex

Novel chiral Er complexes based on both enantiomers of extended (i)PrPyBox (2,6-Bis[4-isopropyl-4,5-dihydrooxazol-2-yl)]pyridine) show strong near-infrared circularly polarized luminescence (CPL) within the 1400 to 1600 nm spectral region under 450 nm irradiation. CPL activity in this region, despite being particularly rare, would open the way to potential applications in the domain, e.g., of fiber-optic telecommunications and free-space long-distance optical communications employing circularly polarized light. Moreover, the long wavelength excitation is advantageous for applications in the field of (circularly polarized) microscopy and bioimaging

Two-Photon Circularly Polarized Luminescence of Chiral Eu Complexes

We report the synthesis of chiral lanthanide complexes with extended π conjugation for efficient circularly polarized luminescence (CPL) via two-photon excitation (2PE). The pyridine bis-oxazoline (PyBox) core provides the chiral Ln3+ environment, while the extension of the conjugated backbone through the pyridine 4-position with a phenylacetylene unit increases the two-photon absorption cross section. This work presents an important step toward the development of chiral systems displaying enhanced nonlinear optical properties, with potential applications in imaging and sensing, as well as in photodynamic therapy due to the selective excitation of molecules within a specific focal volume

Supported tris-triazole ligands for batch and continuous-flow copper-catalyzed huisgen 1,3-dipolar cycloaddition reactions

The lack of supported versions of the tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) ligand, suitable for flow-chemistry applications at scale, prompted us to develop a new route for the immobilization of such tris-triazole chelating units on highly cross-linked polystyrene resins. With this aim, the preparation of the known TBTA-type monomer 3 was optimized to develop a high-yield synthetic sequence, devoid of chromatographic purifications at any stage. Then, bead-type (P7) and monolithic (M7) functional resins were obtained by the easy and scalable suspension-or mold-copolymerization of 3 with divinylbenzene. Both types of materials were found to possess a highly porous morphology and specific surface area in the dry state and could be charged with substantial amounts of Cu(I) or Cu(II) salts. After treatment of the latter with a proper reducing agent, the corresponding supported Cu(I) complexes were tested in the copper-catalyzed alkyne-azide cycloaddition reaction (CuAAC). The immobilized catalysts proved active at room temperature and, in batch and with catalyst loadings as low as 0.6 mol%, afforded quantitative conversions within 20 h. Independent of the alkyne structure, extended use of the supported catalyst in flow was also possible. In the reaction of benzylazide and propargyl alcohol, this allowed a total turnover number larger than 400 to be reached

Chloroplast Genome Sequence of the Moss Torula ruralis: Gene Content, Polymorphism, and Structural Arrangement Relative to Other Green Plant Chloroplast Genomes

Background Tortula ruralis, a widely distributed species in the moss family Pottiaceae, is increasingly used as a model organism for the study of desiccation tolerance and mechanisms of cellular repair. In this paper, we present the chloroplast genome sequence of T. ruralis, only the second published chloroplast genome for a moss, and the first for a vegetatively desiccation-tolerant plant. Results The Tortula chloroplast genome is ~123,500 bp, and differs in a number of ways from that of Physcomitrella patens, the first published moss chloroplast genome. For example, Tortula lacks the ~71 kb inversion found in the large single copy region of the Physcomitrella genome and other members of the Funariales. Also, the Tortula chloroplast genome lacks petN, a gene found in all known land plant plastid genomes. In addition, an unusual case of nucleotide polymorphism was discovered. Conclusions Although the chloroplast genome of Tortula ruralis differs from that of the only other sequenced moss, Physcomitrella patens, we have yet to determine the biological significance of the differences. The polymorphisms we have uncovered in the sequencing of the genome offer a rare possibility (for mosses) of the generation of DNA markers for fine-level phylogenetic studies, or to investigate individual variation within population

The acute myeloid leukemia associated AML1-ETO fusion protein alters the transcriptome and cellular progression in a single-oncogene expressing in vitro induced pluripotent stem cell based granulocyte differentiation model

Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect normal hematopoiesis. The analysis of human AMLs has mostly been performed using end-point materials, such as cell lines and patient derived AMLs that also carry additional contributing mutations. The molecular effects of a single oncogenic hit, such as expression of the AML associated oncoprotein AML1-ETO on hematopoietic development and transformation into a (pre-) leukemic state still needs further investigation. Here we describe the development and characterization of an induced pluripotent stem cell (iPSC) system that allows in vitro differentiation towards different mature myeloid cell types such as monocytes and granulocytes. During in vitro differentiation we expressed the AML1-ETO fusion protein and examined the effects of the oncoprotein on differentiation and the underlying alterations in the gene program at 8 different time points. Our analysis revealed that AML1-ETO as a single oncogenic hit in a non-mutated background blocks granulocytic differentiation, deregulates the gene program via altering the acetylome of the differentiating granulocytic cells, and induces t(8;21) AML associated leukemic characteristics. Together, these results reveal that inducible oncogene expression during in vitro differentiation of iPS cells provides a valuable platform for analysis of aberrant regulation in disease

Heart transplantation and biomarkers: a review about their usefulness in clinical practice

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice

Präferenz für Intuition und Deliberation – Messung und Konsequenzen von affekt- und kognitionsbasiertem Entscheiden

Personen unterscheiden sich darin, ob sie bevorzugt intuitiv oder reflektiv entscheiden (Epstein et al., 1996). Um diese individuellen Unterschiede zu erfassen, wurde ein neues Fragebogenmaß konstruiert, das die Präferenz für Intuition und Deliberation (PID, Betsch, 2004) auf zwei unabhängigen Skalen misst (Präferenz für Intuition und Präferenz für Deliberation). Intuition wird hier als ein rein affektiver Modus verstanden. Deliberation ist konzipiert als reflektiver, kognitionsbasierter Modus. In drei Studien wird die Konstruktion, Überprüfung der Zweidimensionalität und Validierung der Skala anhand von insgesamt über 2500 Versuchspersonen berichtet (Betsch, 2004). Präferenz für Intuition korreliert positiv mit schnellem Entscheiden, Extraversion und Verträglichkeit und ist unabhängig von der Fähigkeit zu logischem Denken. Präferenz für Deliberation korreliert mit Gewissenhaftigkeit, Perfektionismus, Bedürfnis nach Strukturiertheit und ist ebenfalls unabhängig von logischem Denken. Die Validität der Skala und die Implikationen für die Entscheidungsforschung werden in einer weiteren Studie überprüft, die die Krümmung der Nutzenfunktion mit der individuellen Präferenz für Intuition und Deliberation in Verbindung setzt (Schunk & Betsch, im Druck). Die Ergebnisse der Studie zeigen, dass die Entscheidungen intuitiver Menschen das Gefühl, das durch erlebtes Risiko evoziert wurde, integrieren, während dies bei deliberaten Personen nicht der Fall ist. Dies führt zu unterschiedlich gekrümmten Nutzenfunktionen. Neben den Haupteffekten der Strategiepräferenzen werden auch die Interaktion zwischen der individuell bevorzugten und der tatsächlich angewandten Strategie in fünf Studien untersucht (Betsch & Kunz, zur Veröffentlichung eingereicht). Die Ergebnisse der Studien zeigen, dass die Passung zwischen der bevorzugten und tatsächlich verwendeten Strategie (sogenannter decisional fit) den wahrgenommenen Wert des gewählten oder evaluierten Objektes erhöht und dass die Passung als Schutzschild dient gegenüber negativen Emotionen (z.B. Bedauern) nach Entscheidungen mit schlechtem Ausgang. Zusammenfassend umfasst diese Dissertation die Konstruktion und Validierung der Skala zur Erfassung der individuellen Präferenz für Intuition und Deliberation (PID; Betsch, 2004). Weiterhin untersucht sie die Konsequenzen von individuellen Unterschieden in affekt- vs. kognitionsbasiertem Entscheiden auf einen basalen Entscheidungsparameter (die Nutzenfunktion, Schunk & Betsch, im Druck). Außerdem zeigen weitere Studien die Konsequenzen einer Person x Situation Interaktion für zentrale Variablen der Entscheidungsliteratur auf (Wert, Bedauern; Betsch & Kunz, zur Veröffentlichung eingereicht)

Organ specificity in the plant circadian system is explained by different light inputs to the shoot and root clocks

Circadian clocks allow the temporal compartmentalisation of biological processes. In Arabidopsis circadian rhythms display organ specificity but the underlying molecular causes have not been identified. We investigated the mechanisms responsible for the similarities and differences between the clocks of mature shoots and roots in constant conditions and in light:dark cycles. We developed an imaging system to monitor clock gene expression in shoots and light- or dark-grown roots, modified a recent mathematical model of the Arabidopsis clock and used this to simulate our new data. We showed that the shoot and root circadian clocks have different rhythmic properties (period and amplitude) and respond differently to light quality. The root clock was entrained by direct exposure to low-intensity light, even in antiphase to the illumination of shoots. Differences between the clocks were more pronounced in conditions where light is present than in constant darkness, and persisted in the presence of sucrose. We simulated the data successfully by modifying those parameters of a clock model that are related to light inputs. We conclude that differences and similarities between the shoot and root clocks can largely be explained by organ-specific light inputs. This provides mechanistic insight into the developing field of organ-specific clocks