Discovery of potent dihydro-oxazinoquinolinone inhibitors of GuaB for the treatment of tuberculosis.

Tuberculosis is the leading cause of death from an infectious disease, and is caused by Mycobacterium tuberculosis (M.tb). More than 1 billion people worldwide are thought to harbor an M.

Fava Bean Protein Nanofibrils Modulate Cell Membrane Interfaces for Biomolecular Interactions as Unveiled by Atomic Force Microscopy.

Functional amyloids (protein nanofibrils, PNF) synthesized from plant sources exhibit unique physicochemical and nanomechanical properties that could improve food texture. While environmental factors affecting PNFs are well-known, scientific evidence on how cells (focus on the oral cavity) respond to them under physiological conditions is lacking. Self-assembled PNFs synthesized from fava bean whole protein isolate show a strong pH- and solvent-dependent morphology and elasticity modification measured by atomic force microscopy (AFM).

The path to the G protein-coupled receptor structural landscape: Major milestones and future directions.

G protein-coupled receptors (GPCRs) play a crucial role in cell function by transducing signals from the extracellular environment to the inside of the cell. They mediate the effects of various stimuli, including hormones, neurotransmitters, ions, photons, food tastants and odorants, and are renowned drug targets. Advancements in structural biology techniques, including X-ray crystallography and cryo-electron microscopy (cryo-EM), have driven the elucidation of an increasing number of GPCR structures.

[Telemedical care concepts for heart failure: status and future].

Telemedical care concepts provide opportunities to improve the care of patients with chronic heart failure (CHF). The current state of telemedical technologies enables the effective monitoring of the disease. Germany is one of the first European countries with an entitlement to telemedical supporting care for CHF patients.

Enhancing the Capabilities of Continuous Glucose Monitoring With a Predictive App.

Background: Despite abundant evidence demonstrating the benefits of continuous glucose monitoring (CGM) in diabetes management, a significant proportion of people using this technology still struggle to achieve glycemic targets. To address this challenge, we propose the Accu-Chek SmartGuide Predict app, an innovative CGM digital companion that incorporates a suite of advanced glucose predictive functionalities aiming to inform users earlier about acute glycemic situations.

Methods: The app's functionalities, powered by three machine learning models, include a two-hour glucose forecast, a 30-minute low glucose detection, and a nighttime low glucose prediction for bedtime interventions.

Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy.

Purpose: The importance of the DNA damage response in mediating effects of radiotherapy (RT) has galvanized efforts to target this pathway with radiosensitizers. Yet early clinical trials of this approach have failed to yield a benefit in unselected populations. We hypothesized that ataxia-telangiectasia mutated (Atm)-null tumors would demonstrate genotype-specific synergy between RT and an inhibitor of the DNA damage response protein ataxia-telangiectasia and Rad3-related (ATR) kinase.

Towards multicenter β-amyloid PET imaging in mouse models: A triple scanner head-to-head comparison.

Aim: β-amyloid (Aβ) small animal PET facilitates quantification of fibrillar amyloidosis in Alzheimer's disease (AD) mouse models. Thus, the methodology is receiving growing interest as a monitoring tool in preclinical drug trials. In this regard, harmonization of data from different scanners at multiple sites would allow the establishment large collaborative cohorts and may facilitate efficacy comparison of different treatments.

The antimicrobial effectiveness of chlorhexidine and chlorhexidine-silver sulfadiazine-impregnated central venous catheters against the emerging fungal pathogen Candida auris.

Background: Candida auris is an emerging multidrug-resistant fungus associated with catheter-related bloodstream infections. In vitro efficacy of chlorhexidine (CHX) and CHX-silver sulfadiazine-impregnated (CHX-S) antimicrobial central venous catheters (CVCs) against C auris was investigated.

Methods: Minimum inhibitory and bactericidal CHX concentrations were determined against 19 C auris isolates.

Nanodisc Technology: Direction toward Physicochemical Characterization of Chemosensory Membrane Proteins in Food Flavor Research.

Chemosensory membrane proteins such as G-protein-coupled receptors (GPCRs) drive flavor perception of food formulations. To achieve this, a detailed understanding of the structure and function of these membrane proteins is needed, which is often limited by the extraction and purification methods involved. The proposed nanodisc methodology helps overcome some of these existing challenges such as protein stability and solubilization along with their reconstitution from a native cell-membrane environment.

Discovery of a Unique Set of Dog-Seroreactive Proteins Using Nucleic Acid Programmable Protein Array.

Valley Fever (VF), caused by fungi in the genus , is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF.

Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2.

The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity.

Biophysical investigations using atomic force microscopy can elucidate the link between mouthfeel and flavour perception.

Food texture, along with taste and odour, is an important factor in determining food flavour. However, the physiological properties of oral texture perception require greater examination and definition. Here we explore recent trends and perspectives related to mouthfeel and its relevance in food flavour perception, with an emphasis on the biophysical point of view and methods.

A Multimodal Lifestyle Psychosocial Survivorship Program in Young Cancer Survivors: The CARE for CAYA Program-A Randomized Clinical Trial Embedded in a Longitudinal Cohort Study.

Importance: There is a lack of trials examining the effect of counseling interventions for child, adolescent, and younger adult (CAYA) cancer survivors.

Objective: To assess lifestyle habits and the psychosocial situation of CAYAs to determine the efficacy of needs-based interventions in the CARE for CAYA program (CFC-P).

Design, Setting, And Participants: The CFC-P was conducted as a multicenter program in 14 German outpatient clinics, mainly university cancer centers.

Inducing molecular orientation in solution-processed thin films of fluorene-bithiophene-based copolymer: thermal annealing solvent additive.

A deep understanding of the factors influencing the morphology of thin films based on conjugated polymers is essential to boost their performance in optoelectronic devices. Herein, we investigated the electronic structure and morphology of thin films of the copolymer poly(9,9-dioctyl-fluorenyl--bithiophene) (F8T2) in its pristine form as well as samples processed with the solvent additive 1,8-diiodooctane (DIO) or post-processed through thermal annealing treatment. Measurements were carried out using angle-resolved S K-edge NEXAFS (near-edge X-ray absorption fine structure) in total electron yield (TEY) and fluorescence yield (FY) detection modes.

Membrane Permeability in a Large Macrocyclic Peptide Driven by a Saddle-Shaped Conformation.

The effort to modulate challenging protein targets has stimulated interest in ligands that are larger and more complex than typical small-molecule drugs. While combinatorial techniques such as mRNA display routinely produce high-affinity macrocyclic peptides against classically undruggable targets, poor membrane permeability has limited their use toward primarily extracellular targets. Understanding the passive membrane permeability of macrocyclic peptides would, in principle, improve our ability to design libraries whose leads can be more readily optimized against intracellular targets.

A Closed Formalism for Anatomy-Independent Projection and Optimization of Magnetic Stimulation Coils on Arbitrarily Shaped Surfaces.

Introduction: Transcranial magnetic stimulation (TMS) is a popular method for the noninvasive stimulation of neurons in the brain. It has become a standard instrument in experimental brain research and has been approved for a range of diagnostic and therapeutic applications. These applications require appropriately shaped coils.

Development of a Practical Nomogram for Personalized Anemia Management in Patients Treated with Ataxia Telangiectasia and Rad3-related Inhibitor Camonsertib.

Purpose: Camonsertib is a highly selective and potent inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. Dose-dependent anemia is a class-related on-target adverse event often requiring dose modifications. Individual patient risk factors for the development of significant anemia complicate the selection of a "one-size-fits-all" ATR inhibitor (ATRi) dose and schedule, possibly leading to suboptimal therapeutic doses in patients at low risk of anemia.

Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.

To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m, 900 T ms) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations.

Lipid Tales: Optimizing Arylomycin Membrane Anchors.

Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts, no new antibiotic class with activity against Gram-negative bacteria has been approved in over 50 years. LepB inhibitors (LepBi) based on the arylomycin class of natural products are a novel class of antibiotics and function by inhibiting the bacterial type I signal peptidase (SPase) in Gram-negative bacteria. One critical aspect of LepBi development involves optimization of the membrane-anchored lipophilic portion of the molecule.

Eliminating the Imbalanced Mobility Bottlenecks via Reshaping Internal Potential Distribution in Organic Photovoltaics.

The imbalanced carrier mobility remains a bottleneck for performance breakthrough in even those organic solar cells (OSCs) with recorded power conversion efficiencies (PCEs). Herein, a counter electrode doping strategy is proposed to reshape the internal potential distribution, which targets to extract the low mobility carriers at far end. Device simulations reveal that the key of this strategy is to partially dope the active layer with a certain depth, therefore it strengthens the electric field for low mobility carriers near counter electrode region while avoids zeroing the electric field near collection electrode region.