Au → M bonds promote catalytic alkyne hydrofunctionalisation.

The impact of metalloligands on Au catalysed alkyne hydrofunctionalisation is studied. Ambiphilic PMP-type ligands (M = Cu, Ag, Zn) stabilise Au → M bonds including unprecedented Au → Zn interactions. The Lewis acidity of Au increases in the order Cu < Ag < Zn promoting catalytic cycloisomerisation of propargylamide 14.

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany.

Identification of Two Non-Peptidergic Small Molecule Inhibitors of CBX2 Binding to K27 Trimethylated Oligonucleosomes.

The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing trimethylated lysine on histone 3 (H3K27me3) [2] and is overexpressed in metastatic neuroendocrine prostate cancer. [3,4] We implemented a screening strategy using nucleosome substrates to identify inhibitors of CBX2 binding to chromatin.

Evaluation of Pd→B Interactions in Diphosphinoborane Complexes and Impact on Inner-Sphere Reductive Elimination.

The dative Pd→B interaction in a series of DPB Pd and Pd complexes ( DPB =(o-PR C H ) BR', diphosphinoborane) was analyzed using XRD, B NMR spectroscopy and NBO/NLMO calculations. The borane acceptor discriminates between the oxidation state Pd and Pd , stabilizing the latter. Reaction of lithium amides with [( DPB )Pd (4-NO C H )I] chemoselectively yields the C-N coupling product.

A Hexagonal Planar Metal Complex.

A six-coordinate [ML Z ]-type transition-metal complex with a hexagonal planar geometry has been isolated and characterized, extending the scope of six-coordinate metal coordination compounds to those with a geometry beyond octahedral and trigonal prismatic.

Highly efficient palladium-catalysed carbon dioxide hydrosilylation employing PMP ligands.

A series of zero-valent palladium complexes featuring diphosphinometal ligands is reported. The metalloligand in the PMP-type framework (M = LiI, CuI, ZnII) acts as a weak to medium acceptor ligand for palladium. A Pd0→ZnII bond was observed in the solid state and further confirmed by NBO analysis.

Synthesis and properties of heterobimetallic rhodium complexes featuring Li, Cu or Zn as a Lewis acidic metalloligand.

A series of [(PMP)Rh(CO)Cl] complexes was synthesised and the impact of the metalloligands Cu, Li and Zn on the CO stretching band was analysed.

Structural insights into the mechanism of the DEAH-box RNA helicase Prp43.

The DEAH-box helicase Prp43 is a key player in pre-mRNA splicing as well as the maturation of rRNAs. The exact of Prp43 and of all other spliceosomal DEAH-box RNA helicases is still elusive. Here, we report crystal structures of Prp43 complexes in different functional states and the analysis of structure-based mutants providing insights into the unwinding and loading mechanism of RNAs.

Regulation of Prp43-mediated disassembly of spliceosomes by its cofactors Ntr1 and Ntr2.

The DEAH-box NTPase Prp43 disassembles spliceosomes in co-operation with the cofactors Ntr1/Spp382 and Ntr2, forming the NTR complex. How Prp43 is regulated by its cofactors to discard selectively only intron-lariat spliceosomes (ILS) and defective spliceosomes and to prevent disassembly of earlier and properly assembled/wild-type spliceosomes remains unclear. First, we show that Ntr1΄s G-patch motif (Ntr1GP) can be replaced by the GP motif of Pfa1/Sqs1, a Prp43΄s cofactor in ribosome biogenesis, demonstrating that the specific function of Ntr1GP is to activate Prp43 for spliceosome disassembly and not to guide Prp43 to its binding site in the spliceosome.

Isolation and properties of a palladium PBP pincer complex featuring an ambiphilic boryl site.

The palladium diphosphinoboryl pincer [{(o-PPhCH)B}PdI] 8 was prepared from the diphosphinoborane complex 6a. The boryl functionality of the pincer displayed ambiphilic properties allowing: (1) coordination of Lewis basic pyridines to the boryl site and (2) access to palladium diphosphinoborane complex derivatives.

A T-shape diphosphinoborane palladium(0) complex.

The reaction of CpPd(η (3) -C3H5) with the new diphosphinoborane ligand derivative (o-PCy2-C6H4)2BPh (Cy) DPB (Ph) affords the T-shape complex ( (Cy) DPB (Ph) )Pd(0) 9, which was characterized by X-ray analysis.

A spliceosome intermediate with loosely associated tri-snRNP accumulates in the absence of Prp28 ATPase activity.

The precise role of the spliceosomal DEAD-box protein Prp28 in higher eukaryotes remains unclear. We show that stable tri-snRNP association during pre-catalytic spliceosomal B complex formation is blocked by a dominant-negative hPrp28 mutant lacking ATPase activity. Complexes formed in the presence of ATPase-deficient hPrp28 represent a novel assembly intermediate, the pre-B complex, that contains U1, U2 and loosely associated tri-snRNP and is stalled before disruption of the U1/5'ss base pairing interaction, consistent with a role for hPrp28 in the latter.

Impact of the crystallization condition on importin-β conformation.

In eukaryotic cells, the exchange of macromolecules between the nucleus and cytoplasm is highly selective and requires specialized soluble transport factors. Many of them belong to the importin-β superfamily, the members of which share an overall superhelical structure owing to the tandem arrangement of a specific motif, the HEAT repeat. This structural organization leads to great intrinsic flexibility, which in turn is a prerequisite for the interaction with a variety of proteins and for its transport function.

Structural analysis of the spliceosomal RNA helicase Prp28 from the thermophilic eukaryote Chaetomium thermophilum.

Prp28 (pre-mRNA-splicing ATP-dependent RNA helicase 28) is a spliceosomal DEAD-box helicase which is involved in two steps of spliceosome assembly. It is required for the formation of commitment complex 2 in an ATP-independent manner as well as for the formation of the pre-catalytic spliceosome, which in contrast is ATP-dependent. During the latter step, Prp28 is crucial for the integration of the U4/U6·U5 tri-snRNP since it displaces the U1 snRNP and allows the U6 snRNP to base-pair with the 5'-splice site.

The target of the DEAH-box NTP triphosphatase Prp43 in Saccharomyces cerevisiae spliceosomes is the U2 snRNP-intron interaction.

The DEAH-box NTPase Prp43 and its cofactors Ntr1 and Ntr2 form the NTR complex and are required for disassembling intron-lariat spliceosomes (ILS) and defective earlier spliceosomes. However, the Prp43 binding site in the spliceosome and its target(s) are unknown. We show that Prp43 fused to Ntr1's G-patch motif (Prp43_Ntr1GP) is as efficient as the NTR in ILS disassembly, yielding identical dissociation products and recognizing its natural ILS target even in the absence of Ntr1's C-terminal-domain (CTD) and Ntr2.

Structural and functional analysis of the RNA helicase Prp43 from the thermophilic eukaryote Chaetomium thermophilum.

RNA helicases are indispensable for all organisms in each domain of life and have implications in numerous cellular processes. The DEAH-box RNA helicase Prp43 is involved in pre-mRNA splicing as well as rRNA maturation. Here, the crystal structure of Chaetomium thermophilum Prp43 at 2.

Mechanism of the rhodium(III)-catalyzed arylation of imines via C-H bond functionalization: inhibition by substrate.

Rh(III)-catalyzed arylation of imines provides a new method for C-C bond formation while simultaneously introducing an α-branched amine as a functional group. This detailed mechanistic study provides insights for the rational future development of this new reaction. Relevant intermediate Rh(III) complexes have been isolated and characterized, and their reactivities in stoichiometric reactions with relevant substrates have been monitored.

Rhodium(III)-catalyzed arylation of Boc-imines via C-H bond functionalization.

The first rhodium-catalyzed arylation of imines proceeding via C-H bond functionalization is reported. Use of a non-coordinating halide abstractor is important to obtain reactivity. Aryl-branched N-Boc-amines are formed, and a wide range of functionality is compatible with the reaction.

Liquid injection field desorption/ionization of reactive transition metal complexes.

Liquid injection field desorption/ionization (LIFDI) has been applied to identify transition metal complexes that are highly reactive to air and moisture by mass spectrometry. The complexes of nickel and rhodium were supplied as dilute solutions (approximately 0.2 mg ml(-1)) in toluene, tetrahydrofuran or acetonitrile, and were applied onto the field desorption emitter inside the vacuum of the ion source under inert conditions by means of the injection capillary unique to the LIFDI set-up.

Rheohaemapheresis of ophthalmological diseases and diseases of the microcirculation.

Blood rheology was considered to be of limited clinical importance, until extracorporeal technologies enabling the treatment of cellular and plasmatic hyperviscosity syndromes were introduced. However, a wide range of applications, mainly referring to rheologically determined diseases of the microcirculation exists but has so far hardly been taken into consideration. The extension of indications was due to modern technical developments leading to different approaches of secondary separation such as precipitation, ad- or absorption and filtration.

Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure.

Objective: The purpose of this study was to investigate whether long-term therapy with crataegus extract WS 1442 is efficacious as add-on therapy to preexisting diuretic treatment in patients with heart failure with a more advanced stage of the disease (New York Heart Association [NYHA] class III), whether effects are dose dependent, and whether the treatment is safe and well tolerated.

Methods: Exercise capacity was assessed by use of seated bicycle ergometry with incremental workloads. Scores for subjective symptoms and complaints made by the patients were analyzed.

The current state of extracorporeal haemorheotherapy: from haemodilution via cascadefiltration to rheohaemapheresis.

Rheological therapy aims at an improvement of organ perfusion however, it has to be stressed that the tonus of the blood vessels also plays an important role for both the blood distribution and the rheology in the micro- and the macrocirculation. Conventional rheotherapy consists of attempts to influence nutrition and life style, to apply drugs such as purin derivatives, vasodilatating or defibrinising substances and hypervolaemic (using infusion therapy), hypovolaemic, e.g.

The role of rheology in hemapheresis.

Rheological therapy attempts to favorably influence the blood flow mechanics for the treatment of diseases, mainly of the microcirculation but also of the macrocirculation. Hemapheresis, originally used only for the elimination of an excess of cellular or plasmatic components, was shown to also influence the hemorheology favorably. As extracorporeal therapy affects the rheology much more than conventional hemorheotherapy, not only cellular or plasmatic hyperviscosity syndromes but also many more diseases associated with organ perfusion problems due to diseases of the micro- and macrocirculation, especially in the elderly, were and are increasingly considered to be indicated.

[High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure].

The efficacy and tolerance of the standardized hawthorn (crataegus) extract WS 1442 were tested in a multicenter utilization observational study. We monitored 1,011 patients with cardiac insufficiency stage NYHA II, treated with this extract (Crataegutt novo 450, 1 tablet b.i.

[Fibrinolytic therapy of deep vein thrombosis].

Background: The most important complications of deep vein thrombosis are pulmonary embolism and postthrombotic syndrome. While the medicine of lethal pulmonary embolism is reduced to less than 2% by conventional anticoagulation, fibrinolytic therapy aims at a reduction of the greater than 50% incidence of postthrombotic syndrome. The optimal therapeutic regimen concerning risks and effect has not been established yet.