Mechanisms of Lipid-Associated Macrophage Accrual in Metabolically Stressed Adipose Tissue.

Adipose tissue (AT) inflammation, a hallmark of the metabolic syndrome, is triggered by overburdened adipocytes sending out immune cell recruitment signals during obesity development. An AT immune landscape persistent throughout weight loss and regain constitutes an immune-obesogenic memory that hinders long-term weight loss management. Lipid-associated macrophages (LAMs) are emerging as major players in diseased, inflamed metabolic tissues and may be key contributors to an obesogenic memory in AT.

Probing Native CB2 Receptor Mobility in Plasma Membranes of Living Cells by Fluorescence Recovery After Photobleaching.

In this study, we employed a novel fluorescent probe, RO7304924-which selectively targets cannabinoid 2 receptor (CB2R)-to assess the lateral mobility of CB2R within the plasma membrane of Chinese hamster ovary cells stably expressing a functional, untagged receptor variant. Utilizing confocal fluorescence recovery after photobleaching (FRAP), we quantified the diffusion coefficient and mobile fraction of CB2R, thereby demonstrating the efficacy of RO7304924 as an innovative tool for elucidating the dynamics of this major endocannabinoid-binding G protein-coupled receptor. Our present findings highlight the potential of combining advanced ligand-based fluorescent probes with FRAP for future investigations into the biochemical details of CB2R mobility in living cells, and its impact on receptor-dependent cellular processes.

Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders.

Importance: As an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders, but it remains largely unclear which specific cell types and biological mechanisms are involved.

Objective: To determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types.

Role of NaCO as Nucleation Seeds to Accelerate the CO Uptake Kinetics of MgO-Based Sorbents.

There is an urgent need for inexpensive, functional materials that can capture and release CO under industrial conditions. In this context, MgO is a highly promising, earth-abundant CO sorbent. However, despite its favorable carbonation thermodynamics and potential for high gravimetric CO uptakes, MgO-based CO sorbents feature slow carbonation kinetics, limiting their CO uptake during typical industrial contact times.

Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens.

The global rise of antibiotic resistance calls for new drugs against bacterial pathogens. A common approach is to search for natural compounds deployed by microbes to inhibit competitors. Here, we show that the iron-chelating pyoverdines, siderophores produced by environmental spp.

Mechanistic Insights Into Post-Translational α-Keto-β-Amino Acid Formation by a Radical S-Adenosyl Methionine Peptide Splicease.

Radical S-adenosyl methionine enzymes catalyze a diverse repertoire of post-translational modifications in protein and peptide substrates. Among these, an exceptional and mechanistically obscure example is the installation of α-keto-β-amino acid residues by formal excision of a tyrosine-derived tyramine unit. The responsible spliceases are key maturases in a widespread family of natural products termed spliceotides that comprise potent protease inhibitors, with the installed β-residues being crucial for bioactivity.

Challenges in AAV-Based Retinal Gene Therapies and the Role of Magnetic Nanoparticle Platforms.

Retinal diseases, leading to various visual impairments and blindness, are on the rise. However, the advancement of retinal gene therapies offers new hope for treatment of such diseases. Among different vector systems for conferring therapeutic genetic load to retinal cells, adeno-associated viruses (AAVs) have been most intensively explored and have already successfully gained multiple clinical approvals.

A modular and flexible open source cell incubator system for mobile and stationary use.

Culturing living cells requires the maintenance of physiological conditions for extended periods of time. Here, we introduce a versatile and affordable incubation system, addressing the limitations of traditional incubation systems. Conventionally, stationary cell incubators maintain constant temperature and gas levels for cell culturing.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

How Prostate Cancer Growth Patterns Impact Detection and Interreader Agreement on Multiparametric MRI.

Rationale And Objectives: Multiparametric MRI (mpMRI) substantially improves the detection of significant prostate carcinoma (PCa) compared to systematic biopsy. Nevertheless, mpMRI can overlook aggressive forms of PCa. Recent studies showed, that infiltrative growth (INF) has less restricted diffusion.

The Effect of Young People-Assisted, Individualized, Motion-Based Video Games on Physical, Cognitive, and Social Frailty Among Community-Dwelling Older Adults With Frailty: Randomized Controlled Trial.

Background: The aging population highlights the need to maintain both physical and psychological well-being. Frailty, a multidimensional syndrome, increases vulnerability to adverse outcomes. Although physical exercise is effective, adherence among older adults with frailty is often low due to barriers.

Ribosomal peptides with polycyclic isoprenoid moieties.

Isoprenoid modifications of proteins and peptides serve fundamental biological functions and are of therapeutic interest. While C (farnesyl) and C (geranylgeranyl) moieties are prevalent among proteins, known ribosomal peptide prenylations involve shorter-chain units not exceeding farnesyl in size. To our knowledge, cyclized terpene moieties have not been reported from either biomolecule class.

Empirically establishing drug exposure records directly from untargeted metabolomics data.

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action.

Steering research on mRNA splicing in cancer towards clinical translation.

Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome components also 'moonlight' in DNA repair and other cellular processes, making their precise role in cancer difficult to pinpoint. Still, few would deny that dysregulated mRNA splicing is a pervasive feature of most cancers.

Investigation of the Antibacterial Properties of Janus Micromotors Catalytic Propelled by Manganese Dioxide and Hydrogen Peroxide to Reduce Bacterial Density.

Between 2015 and 2017, 90% of Chinese adults were reported to have periodontitis of varying degrees, highlighting the importance of novel, inexpensive, and affordable treatments for the public. The fact that more and more pathogens are becoming resistant to antibiotics further highlights this prevalence. This article addresses a novel micromotor capable of generating reactive oxygen species, as proven by a Fenton-like reaction.

The effect of intra- and inter-fractional motion on target coverage and margins in proton therapy for uveal melanoma.

This study aims to assess the effective lateral margin requirements for target coverage in ocular proton therapy (OPT), considering the unique challenges posed by eye motion and hypofractionation. It specifically addresses the previously unaccounted-for uncertainty contribution of intra-fractional motion, in conjunction with setup uncertainties, on dosimetric determination of lateral margin requirements.The methodology integrates dose calculations from the in-house developed treatment planning system OCULARIS with measured intra-fractional motion, patient models from EyePlan and Monte Carlo (MC) sampling of setup uncertainties.

Inter-individual and inter-regional variability of breast milk antibody reactivity to bacterial lipopolysaccharides.

Breast milk is a vital source of nutrients, prebiotics, probiotics, and protective factors, including antibodies, immune cells and antimicrobial proteins. Using bacterial lipopolysaccharide arrays, we investigated the reactivity and specificity of breast milk antibodies towards microbial antigens, comparing samples from rural Kenya and urban Switzerland. Results showed considerable variability in antibody reactivity both within and between these locations.

Exploring the removal of Spo11 and topoisomerases from DNA breaks in S. cerevisiae by human Tyrosyl DNA Phosphodiesterase 2.

Meiotic recombination is initiated by DNA double-strand breaks (DSBs) created by Spo11, a type-II topoisomerase-like protein that becomes covalently linked to DSB ends. Whilst Spo11 oligos-the products of nucleolytic removal by Mre11-have been detected in several organisms, the lifetime of the covalent Spo11-DSB precursor has not been determined and may be subject to alternative processing. Here, we explore the activity of human Tyrosyl DNA Phosphodiesterase, TDP2-a protein known to repair DNA ends arising from abortive topoisomerase activity-on Spo11 DSBs isolated from S.

Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche's Endocannabinoid System Projects.

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs.

Assessing the Short-Term Efficacy of Digital Cognitive Behavioral Therapy for Insomnia With Different Types of Coaching: Randomized Controlled Comparative Trial.

Background: Digital cognitive behavioral therapy for insomnia (dCBTi) is an effective intervention for treating insomnia. The findings regarding its efficacy compared to face-to-face cognitive behavioral therapy for insomnia are inconclusive but suggest that dCBTi might be inferior. The lack of human support and low treatment adherence are believed to be barriers to dCBTi achieving its optimal efficacy.

Metagenomic Insights Reveal Unrecognized Diversity of Entotheonella in Japanese Theonella Sponges.

Numerous biologically active natural products have been discovered from marine sponges, particularly from Theonella swinhoei, which is known to be a prolific source of natural products such as polyketides and peptides. Recent studies have revealed that many of these natural products are biosynthesized by Candidatus Entotheonella phylotypes, which are uncultivated symbionts within T. swinhoei.