Intrinsic disorder and fuzzy interactions drive multiple functions of HMGB1.

HMGB1, a multitasking protein, is scrutinized here through the lens of the 'fuzzy interactions' driven by its intrinsically disordered regions (IDRs). Although the multiple intracellular and extracellular functions of this protein have been studied for decades, viewing HMGB1 as fuzzy and dynamic provides a novel perspective. Recent breakthroughs emphasize the crucial role of its IDRs, especially the acidic C-terminal tail, in mediating dynamic multivalent interactions.

Hmgb2 improves astrocyte to neuron conversion by increasing the chromatin accessibility of genes associated with neuronal maturation in a proneuronal factor-dependent manner.

Background: Direct conversion of reactive glial cells to neurons is a promising avenue for neuronal replacement therapies after brain injury or neurodegeneration. The overexpression of neurogenic fate determinants in glial cells results in conversion to neurons. For repair purposes, the conversion should ideally be induced in the pathology-induced neuroinflammatory environment.

Next Generation XR Systems-Large Language Models Meet Augmented and Virtual Reality.

Extended reality (XR) is evolving rapidly, offering new paradigms for human-computer interaction. This position paper argues that integrating large language models (LLMs) with XR systems represents a fundamental shift toward more intelligent, context-aware, and adaptive mixed-reality experiences. We propose a structured framework built on three key pillars: first, perception and situational awareness, second, knowledge modeling and reasoning, and third, visualization and interaction.

A spatial- and angle-resolved photoemission spectroscopy beamline based on capillary optics at ASTRID2.

Angle-resolved photoemission spectroscopy (ARPES) with spatial resolution is emerging as a powerful investigative tool for the study of operational mesoscale devices and quantum materials. Here, we introduce AU-SGM4, an extreme ultraviolet beamline based at the ASTRID2 synchrotron, which is designed around an achromatic elliptical capillary optic that focuses the synchrotron light down to a lateral beam spot size of 4 μm. The beamline offers a low photon energy range of 12-150 eV, ideal for probing detailed energy- and momentum-resolved electronic structures of materials.

Insights into how manual therapists incorporate the biopsychosocial-enactive model in the care of individuals with CLBP: a qualitative study.

Background: Chronic low back pain (CLBP) presents a significant challenge for manual therapists. Recent advancements in pain research have highlighted the limitations of the traditional biomedical and biopsychosocial models, prompting the exploration of alternatives. The biopsychosocial-enactive (BPS-E) model has emerged as a promising alternative.

In vitro models of the crosstalk between multiple myeloma and stromal cells recapitulate the mild NF-κB activation observed in vivo.

Multiple myeloma (MM) is linked to chronic NF-κB activity in myeloma cells, but this activity is generally considered a cell-autonomous property of the cancer cells. The precise extent of NF-κB activation and the contributions of the physical microenvironment and of cell-to-cell communications remain largely unknown. By quantitative immunofluorescence, we found that NF-κB is mildly and heterogeneously activated in a fraction of MM cells in human BMs, while only a minority of MM cells shows a strong activation.

Treatment response assessment of acute pyelonephritis: A multi-reader DWI-based MRI approach.

Purpose: To evaluate the diagnostic accuracy of a structured reporting score (SRS) in treatment response assessment for acute pyelonephritis (APN) using a diffusion-weighted imaging (DWI) -based MRI approach. Additionally, we explored the influence of reader experience on the interpretation of SRS and DWI, including lesion conspicuity and measurements of Apparent Diffusion Coefficient (ADC) maps.

Methods: Follow-up DWI-based MRIs of 36 patients treated for APN between September 2021 and June 2023 were retrospectively reviewed by three readers.

Preferential Secretion of Oxidation-Sensitive Proteins by Unconventional Pathways: Why is This Important for Inflammation?

Fidelity of intercellular communication depends on unambiguous interactions between protein ligands and membrane receptors. Most proteins destined to the extracellular space adopt the required three-dimensional shape as they travel through the endoplasmic reticulum (ER), Golgi complex, and other organelles of the exocytic pathway. However, some proteins, many of which are involved in inflammation, avoid this classical secretory route and follow unconventional pathways to leave the cell.

Use of Lomustine and Prednisolone as First-Line Treatment in Canine Multicentric Lymphoma.

Multiagent chemotherapy is considered the most effective treatment for canine high-grade lymphoma; however, due to cost and time requirements, single-agent protocols have also been described. The aim of our study was to evaluate the outcome and prognostic factors of dogs affected by multicentric lymphoma treated with lomustine and prednisolone as first-line treatment. Cases of medium-large-cell multicentric lymphoma treated with lomustine and prednisolone were included in the study.

Hepatic Epithelioid Hemangioendothelioma in a Dog.

A 5-year-old spayed female Breton dog was referred for a thyroid nodule. A total body CT scan evidenced multifocal hepatic nodules. Cytological liver samples were hemodiluted and non-diagnostic.

Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination.

Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under the presumption that it is the primary defense mechanism following vaccination or infection. This perspective, however, can overlook the role of T cells, particularly when antibody levels are low or absent.

The acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with CXCL12.

Chemokine heterodimers activate or dampen their cognate receptors during inflammation. The CXCL12 chemokine forms with the fully reduced (fr) alarmin HMGB1 a physiologically relevant heterocomplex (frHMGB1•CXCL12) that synergically promotes the inflammatory response elicited by the G-protein coupled receptor CXCR4. The molecular details of complex formation were still elusive.

Small transcriptional differences among cell clones lead to distinct NF-κB dynamics.

Transcription factor dynamics is fundamental to determine the activation of accurate transcriptional programs and yet is heterogeneous at a single-cell level, even within homogeneous populations. We asked how such heterogeneity emerges for the nuclear factor κB (NF-κB). We found that clonal populations of immortalized fibroblasts derived from a single mouse embryo display robustly distinct NF-κB dynamics upon tumor necrosis factor ɑ (TNF-ɑ) stimulation including persistent, oscillatory, and weak activation, giving rise to differences in the transcription of its targets.

STAT3-dependent long non-coding RNA Lncenc1 contributes to mouse ES cells pluripotency via stabilizing Klf4 mRNA.

Embryonic stem cells (ESCs) preserve the unique ability to differentiate into any somatic cell lineage while maintaining their self-renewal potential, relying on a complex interplay of extracellular signals regulating the expression/activity of pluripotency transcription factors and their targets. Leukemia inhibitory factor (LIF)-activated STAT3 drives ESCs' stemness by a number of mechanisms, including the transcriptional induction of pluripotency factors such as Klf4 and the maintenance of a stem-like epigenetic landscape. However, it is unknown if STAT3 directly controls stem-cell specific non-coding RNAs, crucial to balance pluripotency and differentiation.

Charge density wave induced nodal lines in LaTe.

LaTe is a non-centrosymmetric material with time reversal symmetry, where the charge density wave is hosted by the Te bilayers. Here, we show that LaTe hosts a Kramers nodal line-a twofold degenerate nodal line connecting time reversal-invariant momenta. We use angle-resolved photoemission spectroscopy, density functional theory with an experimentally reported modulated structure, effective band structures calculated by band unfolding, and symmetry arguments to reveal the Kramers nodal line.

In Situ Exfoliation Method of Large-Area 2D Materials.

2D materials provide a rich platform to study novel physical phenomena arising from quantum confinement of charge carriers. Many of these phenomena are discovered by surface sensitive techniques, such as photoemission spectroscopy, that work in ultra-high vacuum (UHV). Success in experimental studies of 2D materials, however, inherently relies on producing adsorbate-free, large-area, high-quality samples.

Surface Electronic Structure Engineering of Manganese Bismuth Tellurides Guided by Micro-Focused Angle-Resolved Photoemission.

Modification of the electronic structure of quantum matter by ad atom deposition allows for directed fundamental design of electronic and magnetic properties. This concept is utilized in the present study in order to tune the surface electronic structure of magnetic topological insulators based on MnBi Te . The topological bands of these systems are typically strongly electron-doped and hybridized with a manifold of surface states that place the salient topological states out of reach of electron transport and practical applications.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

The interface ofgrown single-layer epitaxial MoSon SrTiO(001) and (111).

SrTiO(STO) is a versatile substrate with a high dielectric constant, which may be used in heterostructures with 2D materials, such as MoS, to induce interesting changes to the electronic structure. STO single crystal substrates have previously been shown to support the growth of well-defined epitaxial single-layer (SL) MoScrystals. The STO substrate is already known to renormalize the electronic bandgap of SL MoS, but the electronic nature of the interface and its dependence on epitaxy are still unclear.

Heparin Protects Human Neural Progenitor Cells from Zika Virus-Induced Cell Death While Preserving Their Differentiation into Mature Neuroglial Cells.

Zika virus (ZIKV) is an arbovirus member of the family that causes severe congenital brain anomalies in infected fetuses. The key target cells of ZIKV infection, human neural progenitor cells (hNPCs), are highly permissive to infection that causes the inhibition of cell proliferation and induces cell death. We have previously shown that pharmaceutical-grade heparin inhibits virus-induced cell death with negligible effects on virus replication in ZIKV-infected hNPCs at the "high" multiplicity of infection (MOI) of 1.