Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision.

The fidelity of immune responses depends on timely controlled and selective mRNA degradation that is largely driven by RNA-binding proteins (RBPs). It remains unclear whether stochastic or directed processes govern the selection of an individual mRNA molecule for degradation. Using human and mouse cells, we show that tristetraprolin (TTP, also known as ZFP36), an essential anti-inflammatory RBP, destabilizes target mRNAs via a hierarchical molecular assembly.

Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy.

Autophagy is a key cellular quality control mechanism. Nutrient stress triggers bulk autophagy, which nonselectively degrades cytoplasmic material upon formation and liquid-liquid phase separation of the autophagy-related gene 1 (Atg1) complex. In contrast, selective autophagy eliminates protein aggregates, damaged organelles and other cargoes that are targeted by an autophagy receptor.

Evidence of microcystin bioaccumulation and its effects on structural alterations in various shrimp (Litopenaeus vannamei Boone, 1931) tissues from shrimp aquaculture in the northern coastal region of East Java, Indonesia.

Microcystins are generated by diverse cyanobacteria in shrimp ponds marked by high nutrient levels. The study examined microcystin-leucine arginine (MC-LR) in the pond water, gills, hepatopancreas, and muscle of shrimp (Litopenaeus vannamei) from shrimp ponds on the northern coast of East Java and its effects on their histological structures. In shrimp ponds dominated by cyanobacteria particularly Microcystis and Oscillatoria, MC-LR levels were high.

Understanding frictional behavior in fascia tissues through tribological modeling and material substitution.

The objective of this study is to develop a reliable tribological model to enable a more thorough investigation of the frictional behavior of fascia tissues connected to non-specific lower back pain. Several models were designed and evaluated based on their coefficient of friction, using a low-frequency, low-load reciprocating motion. The study found that two technical elastomers, layered on PDMS to simulate the fascia and underlying muscle, are suitable substitutes for biological tissue in the model.

The presence and physico-chemical properties of microplastics in seawater, sediment, and several organs of the spotted scat fish (Scatophagus argus, Linnaeus, 1766) collected from different locations along the East Java coast in Indonesia.

A comprehensive study was undertaken to examine the contamination of spotted scat fish (Scatophagus argus) with microplastics (MP) in various locations along the East Java coast of Indonesia. The purpose of this study was to collect detailed information regarding the abundance, color, shape, size, type of polymer, and chemical components of the MP. The findings of this study indicated that MP exhibiting distinct attributes-including a specific fiber type, black coloration, and a size range of 1000- <5000 μm-was most abundant in the gill, stomach, and intestines of spotted scat fish of varying lengths.

A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH). These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3).

A Causal Model of Ion Interference Enables Assessment and Correction of Ratio Compression in Multiplex Proteomics.

Multiplex proteomics using isobaric labeling tags has emerged as a powerful tool for the simultaneous relative quantification of peptides and proteins across multiple experimental conditions. However, the quantitative accuracy of the approach is largely compromised by ion interference, a phenomenon that causes fold changes to appear compressed. The degree of compression is generally unknown, and the contributing factors are poorly understood.

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage.

Post-translational modifications of histones are important regulators of the DNA damage response (DDR). By using affinity purification mass spectrometry (AP-MS) we discovered that genetic suppressor element 1 (GSE1) forms a complex with the HDAC1/CoREST deacetylase/demethylase co-repressor complex. In-depth phosphorylome analysis revealed that loss of GSE1 results in impaired DDR, ATR signalling and γH2AX formation upon DNA damage induction.

Delivery of the Brainshuttle™ amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans.

There are few treatments that slow neurodegeneration in Alzheimer's disease (AD), and while therapeutic antibodies are being investigated in clinical trials for AD treatment, their access to the central nervous system is restricted by the blood-brain barrier. This study investigates a bispecific modular fusion protein composed of gantenerumab, a fully human monoclonal anti- amyloid-beta (Aβ) antibody under investigation for AD treatment, with a human transferrin receptor 1-directed Brainshuttle™ module (trontinemab; RG6102, INN trontinemab). , trontinemab showed a similar binding affinity to fibrillar Aβ and Aβ plaques in human AD brain sections to gantenerumab.

Chemical Acetylation of Ligands and Two-Step Digestion Protocol for Reducing Codigestion in Affinity Purification-Mass Spectrometry.

We present an effective, fast, and user-friendly method to reduce codigestion of bead-bound ligands, such as antibodies or streptavidin, in affinity purification-mass spectrometry experiments. A short preincubation of beads with Sulfo-NHS-Acetate leads to chemical acetylation of lysine residues, making ligands insusceptible to Lys-C-mediated proteolysis. In contrast to similar approaches, our procedure offers the advantage of exclusively using nontoxic chemicals and employing mild chemical reaction conditions.

Advances in RNA Labeling with Trifluoromethyl Groups.

Fluorine labeling of ribonucleic acids (RNA) in conjunction with F NMR spectroscopy has emerged as a powerful strategy for spectroscopic analysis of RNA structure and dynamics, and RNA-ligand interactions. This study presents the first syntheses of 2'-OCF guanosine and uridine phosphoramidites, their incorporation into oligoribonucleotides by solid-phase synthesis and a comprehensive study of their properties. NMR spectroscopic analysis showed that the 2'-OCF modification is associated with preferential C2'-endo conformation of the U and G ribose in single-stranded RNA.

Viscoelastic Response of Elastohydrodynamically Lubricated Compliant Contacts below Glass-Transition Temperature.

The widespread use of polymers in the high-performance engineering applications brings challenges in the field of liquid lubrication in order to separate the rubbing surfaces by the coherent fluid-film thickness relative to not only the inelastic material response of the polymers. The determination of the mechanical properties by the nanoindentation and the dynamic mechanical analysis represents the key methodology to identify the viscoelastic behavior with respect to the intense frequency and temperature dependance exhibited by polymers. The fluid-film thickness was examined by the optical chromatic interferometry on the rotational tribometer in the ball-on-disc configuration.

High Intrinsic Oncogenic Potential in the Myc-Box-Deficient Myc3 Protein.

The proto-oncogene has been intensively studied primarily in vertebrate cell culture systems. Myc transcription factors control fundamental cellular processes such as cell proliferation, cell cycle control and stem cell maintenance. Myc interacts with the Max protein and Myc/Max heterodimers regulate thousands of target genes.

Clp-targeting BacPROTACs impair mycobacterial proteostasis and survival.

The ClpC1:ClpP1P2 protease is a core component of the proteostasis system in mycobacteria. To improve the efficacy of antitubercular agents targeting the Clp protease, we characterized the mechanism of the antibiotics cyclomarin A and ecumicin. Quantitative proteomics revealed that the antibiotics cause massive proteome imbalances, including upregulation of two unannotated yet conserved stress response factors, ClpC2 and ClpC3.

High-resolution structural information of membrane-bound α-synuclein provides insight into the MoA of the anti-Parkinson drug UCB0599.

α-synuclein (αS) is an intrinsically disordered protein whose functional ambivalence and protein structural plasticity are iconic. Coordinated protein recruitment ensures proper vesicle dynamics at the synaptic cleft, while deregulated oligomerization on cellular membranes contributes to cell damage and Parkinson's disease (PD). Despite the protein's pathophysiological relevance, structural knowledge is limited.

Strategies to target the cancer driver MYC in tumor cells.

The MYC oncoprotein functions as a master regulator of cellular transcription and executes non-transcriptional tasks relevant to DNA replication and cell cycle regulation, thereby interacting with multiple proteins. MYC is required for fundamental cellular processes triggering proliferation, growth, differentiation, or apoptosis and also represents a major cancer driver being aberrantly activated in most human tumors. Due to its non-enzymatic biochemical functions and largely unstructured surface, MYC has remained difficult for specific inhibitor compounds to directly address, and consequently, alternative approaches leading to indirect MYC inhibition have evolved.

Mimicking Tumor Cell Heterogeneity of Colorectal Cancer in a Patient-derived Organoid-Fibroblast Model.

Background & Aims: Patient-derived organoid cancer models are generated from epithelial tumor cells and reflect tumor characteristics. However, they lack the complexity of the tumor microenvironment, which is a key driver of tumorigenesis and therapy response. Here, we developed a colorectal cancer organoid model that incorporates matched epithelial cells and stromal fibroblasts.

Unexpected complexity of the ammonia monooxygenase in archaea.

Ammonia oxidation, as the first step of nitrification, constitutes a critical process in the global nitrogen cycle. However, fundamental knowledge of its key enzyme, the copper-dependent ammonia monooxygenase, is lacking, in particular for the environmentally abundant ammonia-oxidizing archaea (AOA). Here the structure of the enzyme is investigated by blue-native gel electrophoresis and proteomics from native membrane complexes of two AOA.

Trophic Transfer of Single-Walled Carbon Nanotubes at the Base of the Food Chain and Toxicological Response.

The potential for trophic transfer of single-walled carbon nanotubes (SWCNTs) was assessed using the green algae and the blue mussel in a series of laboratory experiments. Swanee River Natural Organic Matter (SRNOM)-dispersed SWCNTs were introduced into growing algal cultures. Light microscopical observations, confirmed by scanning electronic microscopy (SEM) and Raman spectroscopy, showed that SWCNT agglomerates adhered to the external algal cell walls and transmission electronic microscopy (TEM) results suggested internalization.

Analysis of Golgi Protein Acetylation Using In Vitro Assays and Parallel Reaction Monitoring Mass Spectrometry.

Acetylation is one of the most abundant post-translational protein modifications that regulates all cellular compartments ranging from chromatin to cytoskeleton and Golgi. The dynamic acetylation of the Golgi stacking protein GRASP55 was shown to regulate Golgi reassembly after mitosis. Here we provide a detailed protocol for the analysis of Golgi acetylation including in vitro assays to detect protein acetylation and mass spectrometry analysis to identify specific acetylation sites and their relative abundance.

amica: an interactive and user-friendly web-platform for the analysis of proteomics data.

Background: Quantitative proteomics has become an increasingly prominent tool in the study of life sciences. A substantial hurdle for many biologists are, however, the intricacies involved in the associated high throughput data analysis.

Results: In order to facilitate this task for users with limited background knowledge, we have developed amica, a freely available open-source web-based software that accepts proteomic input files from different sources.

Robust synthesis of 2'-azido modified RNA from 2'-amino precursors by diazotransfer reaction.

Azides are versatile bioorthogonal reporter moieties that are commonly used for site-specific labeling and functionalization of RNA to probe its biology. The preparation of azido modified nucleic acids by solid-phase synthesis is problematic due to the inherent reactivity of P(III) species with azides according to the Staudinger reaction. Various strategies have been developed to bypass this limitation and are often time-consuming, low-yielding and labor-intensive.

A Proteomic Approach for the Quantification of Posttranslational Protein Lysine Acetylation in Candida albicans.

Candida albicans is a normal component of the human microflora that colonizes mucosal/epithelial surfaces and the gastrointestinal tract as a commensal organism. However, in an immunocompromised host, it can cause life-threatening infections of high mortality and morbidity. Virulence as well as antifungal drug resistance of C.