A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation.

Background: C-reactive protein (CRP) represents a routine diagnostic marker of inflammation. Dissociation of native pentameric CRP (pCRP) into the monomeric structure (mCRP) liberates proinflammatory features, presumably contributing to excessive immune cell activation via unknown molecular mechanisms.

Results: In a multi-translational study of systemic inflammation, we found a time- and inflammation-dependent pCRP dissociation into mCRP.

Discovery of Carbonic Anhydrase 9 as a Novel CLEC2 Ligand in a Cellular Interactome Screen.

Membrane proteins, especially extracellular domains, are key therapeutic targets due to their role in cell communication and associations. Yet, their functions and interactions often remain unclear. This study presents a general method to discover interactions of membrane proteins with immune cells and subsequently to deorphanize their respective receptors.

Probing the Protein Kinases' Cysteinome by Covalent Fragments.

Protein kinases are important drug targets, yet specific inhibitors have been developed for only a fraction of the more than 500 human kinases. A major challenge in designing inhibitors for highly related kinases is selectivity. Unlike their non-covalent counterparts, covalent inhibitors offer the advantage of selectively targeting structurally similar kinases by modifying specific protein side chains, particularly non-conserved cysteines.

Microbiome testing in Europe: navigating analytical, ethical and regulatory challenges.

Background: In recent years, human microbiome research has flourished and has drawn attention from both healthcare professionals and general consumers as the human microbiome is now recognized as having a significant influence on human health. This has led to the emergence of companies offering microbiome testing services. Some of these services are sold directly to the consumer via companies' websites or via medical laboratory websites.

Applying a polysaccharide lyase from to disrupt alginate exopolysaccharide produced by clinical isolates.

Unlabelled: is considered one of the most challenging, drug-resistant, opportunistic pathogens partly due to its ability to synthesize robust biofilms. Biofilm is a mixture of extracellular polymeric substances (EPS) that encapsulates microbial cells, leading to immune evasion, antibiotic resistance, and thus higher risk of infection. In the cystic fibrosis lung environment, undergoes a mucoid transition, defined by overproduction of the exopolysaccharide alginate.

Information needed for optimal immunization related to medical advice: an observational prospective cohort study protocol (INFORMed).

Introduction: Today, accessing information on health issues is easier than ever. However, the flood of information can make decision-making difficult. Information can influence the intention for an action, yet the action often remains unpredictable.

Decoding the Functional Interactome of Non-Model Organisms with PHILHARMONIC.

Protein-protein interaction (PPI) networks are a fundamental resource for modeling cellular and molecular function, and a large and sophisticated toolbox has been developed to leverage their structure and topological organization to predict the functional roles of under-studied genes, proteins, and pathways. However, the overwhelming majority of experimentally-determined interactions from which such networks are constructed come from a small number of well-studied model organisms. Indeed, most species lack even a single experimentally-determined interaction in these databases, much less a network to enable the analysis of cellular function, and methods for computational PPI prediction are too noisy to apply directly.

Anatomy-guided resections for paralimbic tumors in the temporo-insular region: combining tumor and epilepsy surgery concepts.

Object: Tumors in the temporo-mesial region often extend into the insula and vice versa. The present study investigated the results of a surgical strategy that combines principles of tumor and epilepsy surgery.

Methods: We retrospectively analyzed 157 consecutive patients with intrinsic brain tumors in the temporo-mesial region, with varying degrees of extensions into the insula (44 patients, 28.

Physicochemical Properties of Seed Oil Blends and Their Potential for the Creation of Synthetic Oleosomes with Modulated Polarities.

There is an increasing demand within the pharmaceutical and cosmetic industries for biofriendly lipid-based active ingredient delivery systems. Micelles, liposomes, and lipid nanoparticles are currently the most used systems despite their limitations. Oleosomes, also known as lipid droplets, are promising alternatives to the existing strategies.

Shared Decision-Making Communication and Prognostic Misunderstanding in the ICU.

Importance: Surrogate misunderstanding of patient survival prognosis in the intensive care unit (ICU) is associated with poor patient and surrogate outcomes. Shared decision-making (SDM) may reduce misunderstanding.

Objective: To evaluate the association between SDM-aligned communication and prognostic misunderstanding.

Generative Modeling of Molecular Dynamics Trajectories.

Molecular dynamics (MD) is a powerful technique for studying microscopic phenomena, but its computational cost has driven significant interest in the development of deep learning-based surrogate models. We introduce generative modeling of molecular trajectories as a paradigm for learning flexible multi-task surrogate models of MD from data. By conditioning on appropriately chosen frames of the trajectory, we show such generative models can be adapted to diverse tasks such as forward simulation, transition path sampling, and trajectory upsampling.

Community-engaged research: Bringing the science of developmental psychopathology into the real world.

The science of developmental psychopathology has made outstanding progress over the past 40 years in understanding adaptive and maladaptive developmental processes across the life span. Yet most of this work has been researcher driven with little involvement of community partners in the research process, limiting the potential public health significance of our work. To continue to advance the field we must move beyond the physical and conceptual walls of our research laboratories and into the real world.

Squeezing the quantum noise of a gravitational-wave detector below the standard quantum limit.

The Heisenberg uncertainty principle dictates that the position and momentum of an object cannot be simultaneously measured with arbitrary precision, giving rise to an apparent limitation known as the standard quantum limit (SQL). Gravitational-wave detectors use photons to continuously measure the positions of freely falling mirrors and so are affected by the SQL. We investigated the performance of the Laser Interferometer Gravitational-Wave Observatory (LIGO) after the experimental realization of frequency-dependent squeezing designed to surpass the SQL.

Chaotropic Agent-Assisted Supported Lipid Bilayer Formation.

Supported lipid bilayers (SLBs) are useful structures for mimicking cellular membranes, and they can be integrated with a variety of sensors. Although there are a variety of methods for forming SLBs, many of these methods come with limitations in terms of the lipid compositions that can be employed and the substrates upon which the SLBs can be deposited. Here we demonstrate the use of an all-aqueous chaotropic agent exchange process that can be used to form SLBs on two different substrate materials: SiO, which is compatible with traditional SLB formation by vesicle fusion, and AlO, which is not compatible with vesicle fusion.

Microbial Mineralization with for Selective Lithium Nanoparticle Extraction.

Lithium is a critical mineral in a wide range of current technologies, and demand continues to grow with the transition to a green economy. Current lithium mining and extraction practices are often highly ecologically damaging, in part due to the large amount of water and energy they consume. Biomineralization is a natural process that transforms inorganic precursors to minerals.

[Bed confinement in old people-A literature review].

Background: Particularly older people are affected by mobility restrictions and can go through the process of gradually becoming bedridden. This can potentially lead to extensive consequences for the individuals involved, which must be considered in their care.

Aims: To bundle nursing implications related to the phenomenon of being bedridden in the field of long-term care and to provide impulses for research in nursing science.

CD4 T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection.

Immunological priming-in the context of either prior infection or vaccination-elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrated that prior Mtb infection elicited a long-lasting protective response against subsequent Mtb exposure and was CD4 T cell dependent.

[Medication supply and polypharmacy in long-term care : An overview of possible interventions and the question of a functioning concept].

Background: Polypharmacy and the resulting problems lead to considerable consequences for those affected. There are also considerable problems with the medication management.

Objective: Which interventions and programs for optimizing the supply of medication are available for nursing homes and which implementation problems can be expected?

Material And Method: A literature search was carried out for interventional studies in nursing homes in Germany, with a focus on improving medication safety.

S2k-Guideline Non-hormonal Contraception, Part 2: Intrauterine Devices and Sterilization: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015 - 095, January 2024).

This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus.

S2k-Guideline Non-hormonal Contraception, Part 1: Natural Family Planning, Lactational Amenorrhea, Barrier Methods, Coitus Interruptus: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015 - 095, January 2024).

This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus.

Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors.

Macrocyclization of acyclic compounds is a powerful strategy for improving inhibitor potency and selectivity. Here we have optimized 2-aminopyrimidine-based macrocycles to use these compounds as chemical tools for the ephrin kinase family. Starting with a promiscuous macrocyclic inhibitor, , we performed a structure-guided activity relationship and selectivity study using a panel of over 100 kinases.