Deciphering Polymer Interactions in Bioconjugates with Different Architectures by Structural Analysis via Time-resolved Limited Proteolysis Mass Spectrometry.

Therapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer-protein interaction. We deployed limited proteolysis mass spectrometry (LiP-MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon-α2a (IFN). Target conjugates were digested with the specific protease trypsin and a "heavy" 15N-IFN wild type (IFN-WT) for time-resolved quantification of the cleavage dynamics.

The Role of Atrial Fibrillation and Oral Anticoagulation Status in Health-Related Quality of Life 12 Months After Ischemic Stroke or TIA.

Aims: Atrial fibrillation (AF) accounts for about 20% of all ischemic strokes worldwide. It is known that AF impairs health-related quality of life (HRQOL) in the general population, but data on HRQOL in stroke patients with newly diagnosed AF are sparse.

Methods: Post hoc analysis of the prospective, investigator-initiated, multicenter MonDAFIS study (NCT02204267) to analyze whether AF-related oral anticoagulation (OAC), and/or AF-symptom severity are associated with HRQOL after ischemic stroke or transient ischemic attack (TIA).

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Visible-light-induced CO-releasing properties and cytotoxicity of a Ru(II) carbonyl complex containing 2-(pyridin-2-yl)-quinoxaline.

The photo-induced CO-releasing properties of the dark-stable complex [RuCl(CO)L] (L = 2-(pyridin-2-yl)quinoxaline) were investigated under 468 nm light exposure in the presence and absence of biomolecules such as histidine, calf thymus DNA and hen egg white lysozyme. The CO release kinetics were consistent regardless of the presence of these biomolecules, suggesting that they did not influence the CO release mechanism. The quinoxaline ligand demonstrated exceptional cytotoxicity against human acute monocytic leukemia cells (THP-1), with evidence of potential DNA damage ascertained by comet assay, while it remained non-toxic to normal kidney epithelial cells derived from African green monkey (Vero) cell lines.

Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening.

Wilms tumors (WT) are characterized by variable contributions of blastemal, epithelial and stromal elements, reflecting their diverse cellular origins and genetic drivers. In vitro models remain rare, despite a growing need to better characterize tumor biology and evaluate new treatments. Using three approaches, we have now established a large collection of long-term cultures that represent this diversity.

Motor Control on the Move - from Insights in Insects to General Mechanisms.

This review discusses how the nervous system controls the complex body movements keeping animals up and running. In particular, we revisit how research in insects has shed light onto motor control principles that govern movements across the animal kingdom. Starting with the organization and evolution of the insect nervous system, we discuss insights into the neuronal control of behaviors varying in complexity, including escape, flight, crawling, walking, grooming, and courtship.

Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells.

Group 1 innate lymphoid cells (ILCs) encompass NK cells and ILC1s, which have non-redundant roles in host protection against pathogens and cancer. Despite their circulating nature, NK cells can establish residency in selected tissues during ontogeny, forming a distinct functional subset. The mechanisms that initiate, maintain, and regulate the conversion of NK cells into tissue-resident NK (trNK) cells are currently not well understood.

Outcomes of Revision surgery for surgically treated insertional Achilles tendinopathy.

Introduction: There is a clear roadmap for the treatment of primary insertional Achilles tendinopathy (IAT), but data on the outcome of revision surgery is missing. The current study aimed to analyze the outcome following revision surgery for surgically failed IAT.

Material And Methods: Included were patients with IAT revision surgery at a single reference center (01/2010-10/2016) and a follow-up of at least 12 months.

The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation.

Phloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli. , phloroglucinol administration decreases gut and extraintestinal inflammation in murine models of inflammatory bowel disease and systemic infection.

Impaired hemostatic and immune functions of platelets after acute thrombocytopenia.

Background: Platelets are pivotal in maintaining vascular integrity, hemostasis, and immune modulation, with newly generated, immature platelets being the most responsive in fulfilling these tasks. Therefore, the immature platelet fraction provides insights into thrombopoiesis dynamics and clinical prognostication. However, it is currently unclear how immature platelet functions change in settings of acute thrombocytopenia.

Neuro-toxicities of chemo- and immune-therapies in haematologic malignancies: from mechanism to management.

Chemo- and immune therapies administered to treat haematologic malignancies frequently cause neurologic injury. The adverse events range from mild cognitive impairment and headaches to severe conditions such as seizures, stroke and encephalitis. We performed a comprehensive literature review and report the types, mechanisms, management and prevention of neuro-toxicity resulting from these therapies in subjects who develop these toxic effects.

An sRNA overexpression library reveals AbnZ as a negative regulator of an essential translocation module in Caulobacter crescentus.

Small RNAs (sRNAs) play a crucial role in modulating target gene expression through short base-pairing interactions and serve as integral components of many stress response pathways and regulatory circuits in bacteria. Transcriptome analyses have facilitated the annotation of dozens of sRNA candidates in the ubiquitous environmental model bacterium Caulobacter crescentus, but their physiological functions have not been systematically investigated so far. To address this gap, we have established CauloSOEP, a multi-copy plasmid library of C.

SLAM-seq reveals independent contributions of RNA processing and stability to gene expression in African trypanosomes.

Gene expression is a multi-step process that converts DNA-encoded information into proteins, involving RNA transcription, maturation, degradation, and translation. While transcriptional control is a major regulator of protein levels, the role of post-transcriptional processes such as RNA processing and degradation is less well understood due to the challenge of measuring their contributions individually. To address this challenge, we investigated the control of gene expression in Trypanosoma brucei, a unicellular parasite assumed to lack transcriptional control.

Reversible formation of tetraphenylpentalene, a room temperature stable antiaromatic hydrocarbon.

1,3,4,6-Tetraphenylpentalene (PhPn) has been synthesised by chemical oxidation of the corresponding pentalenide complex Mg[PhPn] with iodine. PhPn is a rare example of a room-temperature stable hydrocarbon that is antiaromatic by Hückel's rule and has been fully characterised by NMR and UV-vis spectroscopy, mass spectrometry as well as single-crystal X-ray diffraction. Quantum chemical studies including nucleus-independent chemical shift (NICS) and anisotropy of the induced current density (ACID) calculations showed the existence of an 8π antiaromatic core decorated with four independent 6π aromatic substituents.

Research Priorities for Autonomous Sensory Meridian Response: An Interdisciplinary Delphi Study.

Autonomous Sensory Meridian Response (ASMR) is a multisensory experience most often associated with feelings of relaxation and altered consciousness, elicited by stimuli which include whispering, repetitive movements, and close personal attention. Since 2015, ASMR research has grown rapidly, spanning disciplines from neuroscience to media studies but lacking a collaborative or interdisciplinary approach. To build a cohesive and connected structure for ASMR research moving forwards, a modified Delphi study was conducted with ASMR experts, practitioners, community members, and researchers from various disciplines.

Excimer formation in zinc-phthalocyanine revealed using ultrafast electron diffraction.

The formation of excited dimer states, so called excimers, is an important phenomenon in many organic molecular semiconductor solid state aggregates. In contrast to Frenkel exciton-polarons, an excimer is long-lived and energetically low-lying due to stabilization resulting from a substantial reorganization of the intermolecular geometry. Here, we show that ultrafast electron diffraction can follow the dynamics of solid-state excimer formation in polycrystalline thin films of a molecular semiconductor, revealing both the key reaction modes and the eventual structure of the emitting state.

Toward Intracellular Delivery: Aliphatic Polycarbonates with Pendant Thiol-Reactive Thiosulfonates for Reversible Postpolymerization Modification.

Postpolymerization modifications are valuable techniques for creating functional polymers that are challenging to synthesize directly. This study presents aliphatic polycarbonates with pendant thiol-reactive groups for disulfide formation with mercaptans. The reductive responsive nature of this reaction allows for reversible postpolymerization modifications on biodegradable scaffolds.

Emission-Tunable B←N Lewis Pair-Functionalized Naphthalenes.

Herein, we simultaneously synthesized three different double B←N Lewis pair-functionalized naphthalenes including the asymmetric BNNY and BNNO and the mirror-symmetric BNNR, via a one-pot method. The annulation modes of the B←N Lewis pairs and the substituents on the boron atoms efficiently tune the molecular frontier orbitals and emission colors. α-Position fusion leads to a significant enhancement of the HOMO energy level and a decrease in the HOMO-LUMO gap, while the electron-withdrawing groups attached to the boron atom make the LUMO energy level more stable.

Introducing Degradable Cationic Nanogels Carrying TLR9 Stimulating Oligonucleotides.

Cationic, core-crosslinked nanogel particles are prepared from synthetic biodegradable materials. These fully hydrophilic nanogels offer superior customizability compared to common lipid nanoparticles, thereby circumventing intrinsic immune stimulatory properties. Electrostatic loading allows for complexation of nucleic acids including the immune stimulatory Toll-like receptor 9 (TLR9) agonistCpG-ODN (cytidine-phosphate-guanosine oligodeoxynucleotide).