Protocol for generating splice isoform-specific mouse mutants using CRISPR-Cas9 and a minigene splicing reporter.

Here, we present a protocol to alter the production of alternatively spliced mRNA variants, without affecting the overall gene expression, through CRISPR-Cas9-engineered genomic mutations in mice. We describe steps for designing guide RNA to direct Cas9 endonuclease to consensus splice sites, producing transgenic mice through pronuclear injection, and screening for desired mutations in cultured mammalian cells using a minigene splicing reporter. Splice isoform-specific mouse mutants provide valuable tools for genetic analyses beyond loss-of-function and transgenic alleles.

CO-Tolerant Heterogeneous Ruthenium Catalysts for Efficient Formic Acid Dehydrogenation.

The development of improved and less costly catalysts for dehydrogenation of formic acid (HCOOH) is of general interest for renewable energy technologies involving hydrogen storage and release. Theoretical calculations reveal that ruthenium (Ru) nanoparticles supported on nitrogen-doped carbon should be appropriate catalysts for such transformations. It is predicted that nitrogen doping significantly decreases the formation of CO, but at the same time increases CO tolerance of the catalysts.

A Protocol for Unveiling the Nature of Photocatalytic Hydrogen Evolution Reactions: True Water Splitting or Sacrificial Reagent Acceptorless Dehydrogenation?

Photocatalytic water splitting for hydrogen evolution is a highly topical subject in academic research and a promising approach for sustainable fuel production from solar energy. Due to the mismatched energy diagram of the photosensitizer (especially semiconductor-based materials where band-edge engineering is not trivial) and the redox potential of the half-reactions of water splitting, photocatalytic H generation from water splitting is usually accelerated by the addition of hole scavengers, i.e.

Amino Acid-Based Ionic Liquids-Aided CO Hydrogenation to Methanol.

This study explored the use of amino acid-based ionic liquids to facilitate the conversion of carbon dioxide (CO) into methanol through catalytic hydrogenation. Combining tetrabutylammonium L-argininate (TBA⋅Arg) with the ruthenium Ru-MACHO-BH complex allowed achieving significant yields of methanol under optimized conditions, with a turnover number (TON) up to 700. By systematically varying key reaction parameters, we demonstrated that the TBA⋅Arg ionic liquid promotes the efficient hydrogenation pathway leading to methanol formation, thus offering a sustainable approach to CO valorization.

Combination of nanoparticles with single-metal sites synergistically boosts co-catalyzed formic acid dehydrogenation.

The development of hydrogen technologies is at the heart of a green economy. As prerequisite for implementation of hydrogen storage, active and stable catalysts for (de)hydrogenation reactions are needed. So far, the use of precious metals associated with expensive costs dominates in this area.

Development of a practical formate/bicarbonate energy system.

Liquid (organic) hydrogen carriers ([18H]-dibenzyltoluene, MeOH, formic acid, etc.) form a toolbox for the storage and transport of green hydrogen, which is crucial for the implementation of renewable energy technologies. Simple organic salts have been scarcely investigated for this purpose, despite many advantages such as low cost and minor toxicity, as well as easy handling.

Bovine medicine: Whats´s your diagnosis?

Two Angus calves housed in the Swiss Alps for two months were presented with brisket edema, jugular distension, and diarrhea. Hematological and biochemical examination included elevated concentration of erythrocytes and increased activity of liver enzymes. Ultrasonography revealed small amount of pleural effusion hepatomegaly and congested caudal vena cava.

Unprecedented MoS cluster-catalyzed radical C-C cross-coupling reactions of aryl alkynes and acrylates.

A new method for the generation of benzyl radicals from terminal aromatic alkynes has been developed, which allows the direct cross coupling with acrylate derivatives. Our additive-free protocol employs air-stable diamino MoS cubane-type cluster catalysts in the presence of hydrogen. A sulfur-centered cluster catalysis mechanism for benzyl radical formation is proposed based on catalytic and stoichiometric experiments.

Evaluation of the Audicor Acoustic Cardiography Device as a Diagnostic Tool in Horses with Mitral or Aortic Valve Insufficiency.

Mitral and aortic valve insufficiencies have been commonly reported in horses. The objective of this study was to establish the use of acoustic cardiography (Audicor) in horses with aortic (AI) or mitral valve insufficiency (MI). A total of 17 healthy horses, 18 horses with AI, and 28 horses with MI were prospectively included.

First steps of learning analytics in a blended learning general practice curriculum at Saarland University - a quantitative approach.

Objectives: Medical education has been revolutionized by the growing importance of digital learning. Little is known about students' online study behaviour and its relationship with exam performance. This quantitative study analyses and describes students' digital learning behaviours in a blended learning curriculum for General practice at Saarland University, Germany.

Improving compliance with isolation measures in the operating room: a prospective simulation study comparing the effectiveness and costs of simulation-based training vs video-based training.

Background: Different isolation measures are required according to the routes of transmission of pathogens. Few studies have compared different forms of hygiene training in terms of efficiency and/or improvement of perception towards hygiene measures. This study aimed to evaluate the benefits of different forms of isolation training in the operating room, and their respective effects on the perception of hygiene measures by comparing simulation training with video-based training.

Atomically Dispersed Cobalt/Copper Dual-Metal Catalysts for Synergistically Boosting Hydrogen Generation from Formic Acid.

The development of practical materials for (de)hydrogenation reactions is a prerequisite for the launch of a sustainable hydrogen economy. Herein, we present the design and construction of an atomically dispersed dual-metal site Co/Cu-N-C catalyst allowing significantly improved dehydrogenation of formic acid, which is available from carbon dioxide and green hydrogen. The active catalyst centers consist of specific CoCuN moieties with double-N-bridged adjacent metal-N clusters decorated on a nitrogen-doped carbon support.

A Frizzled4-LRP5 agonist promotes blood-retina barrier function by inducing a Norrin-like transcriptional response.

Norrin (NDP) and WNT7A/B induce and maintain the blood-brain and blood-retina barrier (BBB, BRB) by stimulating the Frizzled4-LDL receptor related protein 5/6 (FZD4-LRP5/6) complex to induce beta-catenin-dependent signaling in endothelial cells (ECs). Recently developed agonists for the FZD4-LRP5 complex have therapeutic potential in retinal and neurological diseases. Here, we use the tetravalent antibody modality F4L5.

What competencies do European general practice trainees value the most? A prioritisation exercise using a Delphi-informed approach.

General Practice has changed over the past decade. Expansion of clinicians' roles may create uncertainty, stress, and overload - particular for those at the start of their career. The WONCA Europe network for medical education, EURACT, has published competency-based aims and requirements for speciality training in general practice.

Carbon neutral hydrogen storage and release cycles based on dual-functional roles of formamides.

The development of alternative clean energy carriers is a key challenge for our society. Carbon-based hydrogen storage materials are well-suited to undergo reversible (de)hydrogenation reactions and the development of catalysts for the individual process steps is crucial. In the current state, noble metal-based catalysts still dominate this field.

BRD4 inhibition sensitizes diffuse large B-cell lymphoma cells to ferroptosis.

Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, is characterized by an aggressive clinical course. In approximately one-third of patients with DLBCL, first-line multiagent immunochemotherapy fails to produce a durable response. Molecular heterogeneity and apoptosis resistance pose major therapeutic challenges in DLBCL treatment.

{μ-2,2'-(Ethane-1,2-di-yl)bis-[4,6-bis-(tri-methyl-sil-yl)-1,3-di-hydro-cyclo-penta-[]pyrrol-5-one]}bis-[tri-carbonyl-iron(0)].

The binuclear title compound, [Fe(CHNOSi)(CO)], consists of two central iron(0) atoms, each of them surrounded by a cyclo-penta-dienone moiety and three carbonyl ligands in a three-legged piano-stool shape. Furthermore, the bis-(cyclo-penta-dienone) ligand acts as a bridge between the two metal atoms.

A tug of war between DCC and ROBO1 signaling during commissural axon guidance.

Dynamic and coordinated axonal responses to changing environments are critical for establishing neural connections. As commissural axons migrate across the CNS midline, they are suggested to switch from being attracted to being repelled in order to approach and to subsequently leave the midline. A molecular mechanism that is hypothesized to underlie this switch in axonal responses is the silencing of Netrin1/Deleted in Colorectal Carcinoma (DCC)-mediated attraction by the repulsive SLIT/ROBO1 signaling.

Efficient Synthesis of Novel Plasticizers by Direct Palladium-Catalyzed Di- or Multi-carbonylations.

Diesters are of fundamental importance in the chemical industry and are used for many applications, e.g. as plasticizers, surfactants, emulsifiers, and lubricants.

Manganese Promoted (Bi)carbonate Hydrogenation and Formate Dehydrogenation: Toward a Circular Carbon and Hydrogen Economy.

We report here a feasible hydrogen storage and release process by interconversion of readily available (bi)carbonate and formate salts in the presence of naturally occurring α-amino acids. These transformations are of interest for the concept of a circular carbon economy. The use of inorganic carbonate salts for hydrogen storage and release is also described for the first time.

Improved CO Capture and Catalytic Hydrogenation Using Amino Acid Based Ionic Liquids.

A series of alkyl ammonium (or imidazolium) based ionic liquids was tested as novel and potentially green absorbent for CO capture and utilization. By exploiting various amino acids as counter ions for ionic liquids, CO capture and hydrogenation to formate occur with high activity and excellent productivity utilizing arginine. The reaction was easily scalable without any significant drop in formate production, and the catalyst was reused for five consecutive runs leading to an overall TON of 12,741 for the formation of formate salt.

A practical concept for catalytic carbonylations using carbon dioxide.

The rise of CO in atmosphere is considered as the major reason for global warming. Therefore, CO utilization has attracted more and more attention. Among those, using CO as C1-feedstock for the chemical industry provides a solution.

An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation.

Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated.