Structure and function of IWS1 in transcription elongation.

Transcription elongation by RNA polymerase II is a tightly regulated process that requires coordinated interactions between elongation factors. IWS1 (Interacts with SPT6) has been implicated as a core elongation factor, but its molecular role remains unclear. We show that the intrinsically disordered C-terminal region of IWS1 contains short linear motifs (SLiMs) that multivalently engage the elongation machinery.

USP37 prevents premature disassembly of stressed replisomes by TRAIP.

The eukaryotic replisome, which consists of the CDC45-MCM2-7-GINS (CMG) helicase, replicative polymerases, and several accessory factors, sometimes encounters proteinaceous obstacles that threaten genome integrity. These obstacles are targeted for removal or proteolysis by the E3 ubiquitin ligase TRAIP, which associates with the replisome. However, TRAIP must be carefully regulated to avoid inappropriate ubiquitylation and disassembly of the replisome.

The NHEJ machinery is translocated off DNA ends to enable resection.

Error-prone non-homologous end joining (NHEJ) and homologous recombination (HR) compete to repair DNA double strand breaks [1, 2, 3]. Given that NHEJ factors such as Ku and DNA-PKcs are rapidly recruited to DSBs and sterically occlude ends, they must be removed to enable 5 DNA end resection, the commitment step of HR. While resection is well characterized, how the NHEJ machinery is displaced from DNA ends has remained poorly understood.

EndoMAP.v1 charts the structural landscape of human early endosome complexes.

Early or sorting endosomes are dynamic organelles that play key roles in proteome control by triaging plasma membrane proteins for either recycling or degradation in the lysosome. These events are coordinated by numerous transiently associated regulatory complexes and integral membrane components that contribute to organelle identity during endosome maturation. Although a subset of the several hundred protein components and cargoes known to associate with endosomes have been studied at the biochemical and/or structural level, interaction partners and higher-order molecular assemblies for many endosomal components remain unknown.

Investigation of the Degree of Functionalization and Colloidal Stability of Shell-by-Shell Functionalized TiO Nanoparticles as a Function of Different Phosphonic Acid Chain Lengths.

In this work, a series of Shell-by-Shell (SbS)-functionalized colloidal systems consisting of 6 nm TiO anatase nanoparticles (NPs), one of the phosphonic acids (PAs) propylphosphonic acid (PAC), hexylphosphonic acid (PAC), dodecylphosphonic acid (PAC), tetradecylphosphonic acid (PAC), hexadecylphosphonic acid (PAC), octadecylphosphonic acid (PAC) and the amphiphile sodium dodecylbenzenesulfonate (SDBS) were prepared, resulting in TiO-PAC@SDBS (X = 3, 6, 12, 14, 16, or 18) NPs dispersed in deionized water (DIW). During the whole functionalization process, the NPs were subjected to thermogravimetric analysis (TGA) to gain insights into their degree of functionalization and respective thermal stability. In addition, the colloidal stability of the NPs as a function of PA chain length was analyzed by analytical ultracentrifugation (AUC).

A fundamental approach to buoyant density determination by DGE-AUC.

Density gradient equilibrium analytical ultracentrifugation (DGE-AUC) was first introduced in 1957. The method saw significant use over the following decade. Since then, DGE-AUC has been used by polymer and genomic DNA fields.

Separation of Indium Phosphide/Zinc Sulfide Core-Shell Quantum Dots from Shelling Byproducts through Multistep Agglomeration.

Semiconductor quantum dots (QDs) possess unique electronic and optical properties, making them promising candidates for applications in light-emitting diodes, solar cells, bioimaging, and photocatalysis. Precise control over their size, shape, and chemical and electronic structure is crucial to ensure the desired functional properties and optimize device performance. However, challenges in QD synthesis and post-synthesis modification persist, especially in large-scale production.

The aPBP-type cell wall synthase PBP1b plays a specialized role in fortifying the division site against osmotic rupture.

A multi-protein system called the divisome promotes bacterial division. This apparatus synthesizes the peptidoglycan (PG) cell wall layer that forms the daughter cell poles and protects them from osmotic lysis. In the model Gram-negative bacterium , PG synthases called class A penicillin-binding proteins (aPBPs) have been proposed to play crucial roles in division.

Characterization of the two-dimensional length and diameter distributions of gold nanorods by size exclusion chromatography.

Access to complex multidimensional property distributions of nanoparticle systems is indispensable for the understanding of their synthesis, processing and application in modern production technologies. Plasmonic gold nanorods are a system of particular interest due to their shape-dependent localized surface plasmon resonance. In this study, we show how the optical back coupling technique, previously developed for the analysis of sedimentation coefficient-resolved extinction spectra derived from analytical ultracentrifugation experiments, can be transferred to standard laboratory equipment, namely size exclusion chromatography.

Predictomes, a classifier-curated database of AlphaFold-modeled protein-protein interactions.

Protein-protein interactions (PPIs) are ubiquitous in biology, yet a comprehensive structural characterization of the PPIs underlying cellular processes is lacking. AlphaFold-Multimer (AF-M) has the potential to fill this knowledge gap, but standard AF-M confidence metrics do not reliably separate relevant PPIs from an abundance of false positive predictions. To address this limitation, we used machine learning on curated datasets to train a structure prediction and omics-informed classifier (SPOC) that effectively separates true and false AF-M predictions of PPIs, including in proteome-wide screens.

EndoMAP.v1, a Structural Protein Complex Landscape of Human Endosomes.

Early/sorting endosomes are dynamic organelles that play key roles in proteome control by triaging plasma membrane proteins for either recycling or degradation in the lysosome. These events are coordinated by numerous transiently-associated regulatory complexes and integral membrane components that contribute to organelle identity during endosome maturation. While a subset of the several hundred protein components and cargoes known to associate with endosomes have been studied at the biochemical and/or structural level, interaction partners and higher order molecular assemblies for many endosomal components remain unknown.

Analysis of Giant-Shell CdSe/CdS Quantum Dots via Analytical Ultracentrifugation Combined with Spectrally Resolved Photoluminescence.

Knowledge of the structure-property relationships of functional nanomaterials, including, for example, their size- and composition-dependent photoluminescence (PL) and particle-to-particle variations, is crucial for their design and reproducibility. Herein, the Angstrom-resolution capability of an analytical ultracentrifuge combined with an in-line multiwavelength emission detection system (MWE-AUC) for measuring the sedimentation coefficient-resolved spectrally corrected PL spectra of dispersed nanoparticles is demonstrated. The capabilities of this technique are shown for giant-shell CdSe/CdS quantum dots (g-QDs) with a PL quantum yield (PL QY) close to unity capped with oleic acid and oleylamine ligands.

Evaluating optic system compression in sellar tumors: A novel application of quantitative pupillometry.

Introduction: Tumorous growths in the sellar region pose significant clinical challenges due to their proximity to critical visual structures such as the optic chiasm and optic nerves. Given their proximity to the optic system, these tumors are often diagnosed due to a progressive decrease in visual acuity. Thus, surgical intervention is crucial to prevent irreversible damage, as timely decompression can halt the progression of edema and subsequent optic atrophy.

TTF2 promotes replisome eviction from stalled forks in mitosis.

When cells enter mitosis with under-replicated DNA, sister chromosome segregation is compromised, which can lead to massive genome instability. The replisome-associated E3 ubiquitin ligase TRAIP mitigates this threat by ubiquitylating the CMG helicase in mitosis, leading to disassembly of stalled replisomes, fork cleavage, and restoration of chromosome structure by alternative end-joining. Here, we show that replisome disassembly requires TRAIP phosphorylation by the mitotic Cyclin B-CDK1 kinase, as well as TTF2, a SWI/SNF ATPase previously implicated in the eviction of RNA polymerase from mitotic chromosomes.

STK19 positions TFIIH for cell-free transcription-coupled DNA repair.

In transcription-coupled nucleotide excision repair (TC-NER), stalled RNA polymerase II (RNA Pol II) binds CSB and CRL4, which cooperate with UVSSA and ELOF1 to recruit TFIIH. To explore the mechanism of TC-NER, we recapitulated this reaction in vitro. When a plasmid containing a site-specific lesion is transcribed in frog egg extract, error-free repair is observed that depends on CSB, CRL4, UVSSA, and ELOF1.

Shell-by-Shell functionalized nanoparticles as radiosensitizers and radioprotectors in radiation therapy of cancer cells and tumor spheroids.

Shell-by-Shell (SbS)-functionalized NPs can be tailor-made by combining a metal oxide NP core of choice with any desired phosphonic acids and amphiphiles as 1st or 2nd ligand shell building blocks. The complementary composition of such highly hierarchical structures makes them interesting candidates for various biomedical applications, as certain active ingredients can be incorporated into the structure. Here, we used TiO and CoFeO NPs as drug delivery tools and coated them with a hexadecylphosphonic acid and with hexadecyl ammonium phenolates (caffeate, p-coumarate, ferulate), that possess anticancer as well as antioxidant properties.

USP37 prevents premature disassembly of stressed replisomes by TRAIP.

The E3 ubiquitin ligase TRAIP associates with the replisome and helps this molecular machine deal with replication stress. Thus, TRAIP promotes DNA inter-strand crosslink repair by triggering the disassembly of CDC45-MCM2-7-GINS (CMG) helicases that have converged on these lesions. However, disassembly of single CMGs that have stalled temporarily would be deleterious, suggesting that TRAIP must be carefully regulated.

Electrohydraulic musculoskeletal robotic leg for agile, adaptive, yet energy-efficient locomotion.

Robotic locomotion in unstructured terrain demands an agile, adaptive, and energy-efficient architecture. To traverse such terrains, legged robots use rigid electromagnetic motors and sensorized drivetrains to adapt to the environment actively. These systems struggle to compete with animals that excel through their agile and effortless motion in natural environments.

STK19 positions TFIIH for cell-free transcription-coupled DNA repair.

In transcription-coupled repair, stalled RNA polymerase II (Pol II) is recognized by CSB and CRL4, which co-operate with UVSSSA and ELOF1 to recruit TFIIH for nucleotide excision repair (TC-NER). To explore the mechanism of TC-NER, we recapitulated this reaction . When a plasmid containing a site-specific lesion is transcribed in frog egg extract, error-free repair is observed that depends on CSB, CRL4, UVSSA, and ELOF1.

screening identifies SHPRH as a novel nucleosome acidic patch interactor.

Unlabelled: Nucleosomes are the fundamental unit of eukaryotic chromatin. Diverse factors interact with nucleosomes to modulate chromatin architecture and facilitate DNA repair, replication, transcription, and other cellular processes. An important platform for chromatin binding is the H2A-H2B acidic patch.

Development of an advanced multiwavelength emission detector for the analytical ultracentrifuge.

An advanced design of the analytical ultracentrifuge with multiwavelength emission detection (MWE-AUC) is presented which offers outstanding performance concerning the spectral resolution and range flexibility as well as the quality of the data acquired. The excitation by a 520 nm laser is complemented with a 405 nm laser. An external spectrograph with three switchable tunable gratings permits optimisation of the spectral resolution in an order of magnitude range while keeping the spectral region broad.