Highly diastereoselective synthesis of aza-diels-alder reaction of danishefsky diene wiht glyoxylate imines

Aza-Diels-Alder reaction is an exceptionally powerful synthetic method for the construction of six-membered nitrogen-heterocycles.[1-3] The reaction of Danishefsky's diene 1 with iminoacetates 2 (imines of glyoxylates) provides a convenient protocol for the synthesis of pipiridone adducts 3 (Scheme 1). In this context, we have performed the synthesis of various cycloadducts, precursors of a wide variety of chiral piperidines with potential use as non-natural amino acids or as precursors of biologically active compounds, including iminosugars (glycomimetics)

Hypertiling -- a high performance Python library for the generation and visualization of hyperbolic lattices

Hypertiling is a high-performance Python library for the generation and visualization of regular hyperbolic lattices embedded in the Poincar\'e disk model. Using highly optimized, efficient algorithms, hyperbolic tilings with millions of vertices can be created in a matter of minutes on a single workstation computer. Facilities including computation of adjacent vertices, dynamic lattice manipulation, refinements, as well as powerful plotting and animation capabilities are provided to support advanced uses of hyperbolic graphs. In this manuscript, we present a comprehensive exploration of the package, encompassing its mathematical foundations, usage examples, applications, and a detailed description of its implementation.Comment: 52 pages, 20 figure

Migrant participation in Norwegian health care. A qualitative study using key informants

Background Little is known about how migrants adapt to first-world public health systems. In Norway, patients are assigned a registered general practitioner (RGP) to provide basic care and serve as gatekeeper for other medical services. Objectives: To explore determinants of migrant compliance with the RGP scheme and obstacles that migrants may experience. Methods: Individuals in leadership positions within migrant organizations for the 13 largest migrant populations in Norway in 2008 participated in this qualitative study. Semi-structured interviews, with migrants serving as key informants, were used to elucidate possible challenges migrant patients face in navigating the local primary health-care system. Conversations were structured using an interview guide covering the range of challenges that migrant patients meet in the health-care system. Results: According to informants, integration into the RGP scheme and adequacy of patient-physician communication varies according to duration of stay in Norway, the patient's country of origin, the reason for migration, health literacy, intention to establish permanent residence in Norway, language proficiency, and comprehension of information received about the health system. Informants noted as obstacles: doctor-patient interaction patterns, conflicting ideas about the role of the doctor, and language and cultural differences. In addressing noted obstacles, one strategy would be to combine direct intervention by migrant associations with indirect intervention via the public-health system

The ALF (Algorithms for Lattice Fermions) project release 2.0. Documentation for the auxiliary-field quantum Monte Carlo code

The Algorithms for Lattice Fermions package provides a general code for the finite-temperature and projective auxiliary-field quantum Monte Carlo algorithm. The code is engineered to be able to simulate any model that can be written in terms of sums of single-body operators, of squares of single-body operators and single-body operators coupled to a bosonic field with given dynamics. The package includes five pre-defined model classes: SU(N) Kondo, SU(N) Hubbard, SU(N) t-V and SU(N) models with long range Coulomb repulsion on honeycomb, square and N-leg lattices, as well as $Z_2$ unconstrained lattice gauge theories coupled to fermionic and $Z_2$ matter. An implementation of the stochastic Maximum Entropy method is also provided. One can download the code from our Git instance at https://git.physik.uni-wuerzburg.de/ALF/ALF/-/tree/ALF-2.0 and sign in to file issues.Comment: 121 pages, 11 figures. v3: quick tutorial section added, typos corrected, etc. Submission to SciPost. arXiv admin note: text overlap with arXiv:1704.0013

Uncoupling of ATP-Mediated Calcium Signaling and Dysregulated Interleukin-6 Secretion in Dendritic Cells by Nanomolar Thimerosal

Dendritic cells (DCs), a rare cell type widely distributed in the soma, are potent antigen-presenting cells that initiate primary immune responses. DCs rely on intracellular redox state and calcium (Ca(2+)) signals for proper development and function, but the relationship between these two signaling systems is unclear. Thimerosal (THI) is a mercurial used to preserve vaccines and consumer products, and is used experimentally to induce Ca(2+) release from microsomal stores. We tested adenosine triphosphate (ATP)-mediated Ca(2+) responses of DCs transiently exposed to nanomolar THI. Transcriptional and immunocytochemical analyses show that murine myeloid immature DCs (IDCs) and mature DCs (MDCs) express inositol 1,4,5-trisphosphate receptor (IP(3)R) and ryanodine receptor (RyR) Ca(2+) channels, known targets of THI. IDCs express the RyR1 isoform in a punctate distribution that is densest near plasma membranes and within dendritic processes, whereas IP(3)Rs are more generally distributed. RyR1 positively and negatively regulates purinergic signaling because ryanodine (Ry) blockade a) recruited 80% more ATP responders, b) shortened ATP-mediated Ca(2+) transients > 2-fold, and c) produced a delayed and persistent rise (≥ 2-fold) in baseline Ca(2+). THI (100 nM, 5 min) recruited more ATP responders, shortened the ATP-mediated Ca(2+) transient (≥ 1.4-fold), and produced a delayed rise (≥ 3-fold) in the Ca(2+) baseline, mimicking Ry. THI and Ry, in combination, produced additive effects leading to uncoupling of IP(3)R and RyR1 signals. THI altered ATP-mediated interleukin-6 secretion, initially enhancing the rate of cytokine secretion but suppressing cytokine secretion overall in DCs. DCs are exquisitely sensitive to THI, with one mechanism involving the uncoupling of positive and negative regulation of Ca(2+) signals contributed by RyR1

An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles

Peptide hormones and neuropeptides encompass a large class of bioactive peptides that regulate physiological processes like anxiety, blood glucose, appetite, inflammation and blood pressure. Here, we execute a focused discovery strategy to provide an extensive map of O-glycans on peptide hormones. We find that almost one third of the 279 classified peptide hormones carry O-glycans. Many of the identified O-glycosites are conserved and are predicted to serve roles in proprotein processing, receptor interaction, biodistribution and biostability. We demonstrate that O-glycans positioned within the receptor binding motifs of members of the neuropeptide Y and glucagon families modulate receptor activation properties and substantially extend peptide half-lives. Our study highlights the importance of O-glycosylation in the biology of peptide hormones, and our map of O-glycosites in this large class of biomolecules serves as a discovery platform for an important class of molecules with potential opportunities for drug designs. O-glycosylation is an abundant post-translational modification but its relevance for bioactive peptides is unclear. Here, the authors detect O-glycans on almost one third of the classified peptide hormones and show that O-glycosylation can modulate peptide half-lives and receptor activation properties.This work was supported by the Novo Nordisk Foundation, the Lundbeck Foundation, Danish National Research Foundation Grant DNRF107

Phytophthora species and oak decline - can a weak competitor cause significant root damage in a nonsterilized acidic forest soil?

Phytophthora species in general, and P. quercina in particular, have been suggested in several studies to be a contributing factor to the problem of oak decline in Europe. Although Phytophthora species are generally regarded as weak competitors, few studies of the pathogenicity of species causing root rot on oaks have hitherto been performed in natural, nonsterilized forest soils. This study describes the effects of seven southern Swedish isolates of P. quercina and one isolate of P. cactorum on root vitality of Quercus robur seedlings grown in a natural, nonsterilized, acidic forest soil. The pathogenicity of P. quercina and P. cactorum were tested using a soil infestation test. The climatic conditions applied were an attempt to simulate summer conditions in southern Sweden. Both species of Phytophthora caused a significant dieback of fine roots, and necrotic lesions on coarser roots, of Q. robur seedlings. Total and live root lengths were significantly lower in infected seedlings than in controls. No significant effects of Phytophthora on above-ground growth or leaf nutrient concentration were found. The results demonstrate that P. quercina and P. cactorum can cause substantial root dieback of seedlings of Q. robur in natural, acidic forest soils in competition with the inhabiting soil microflora under a mesic water regime

Translational research in acute lung injury and pulmonary fibrosis attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair

© 2015 the American Physiological Society Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands on bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors, and signaling targets in wild-type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested by using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double-transgenic (DTG) Rosa26rtTA/+;tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from postnatal days (PN) 1 through PN105. Female single-transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0 U/kg). Fgfr2b ligands were attenuated either throughout injury (days 0-11; days 0-28) or during later stages (days 6-28 and 14-28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin-induced lung injury in mice