A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson's disease.

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking.

Stress-Dependent Optical Extinction in Low-Pressure Chemical Vapor Deposition Silicon Nitride Measured by Nanomechanical Photothermal Sensing.

Understanding optical absorption in silicon nitride is crucial for cutting-edge technologies like photonic integrated circuits, nanomechanical photothermal infrared sensing and spectroscopy, and cavity optomechanics. Yet, the origin of its strong dependence on the film deposition and fabrication process is not fully understood. This Letter leverages nanomechanical photothermal sensing to investigate optical extinction κ at a 632.

Trifunctional sphingomyelin derivatives enable nanoscale resolution of sphingomyelin turnover in physiological and infection processes via expansion microscopy.

Sphingomyelin is a key molecule of sphingolipid metabolism, and its enzymatic breakdown is associated with various infectious diseases. Here, we introduce trifunctional sphingomyelin derivatives that enable the visualization of sphingomyelin distribution and sphingomyelinase activity in infection processes. We demonstrate this by determining the activity of a bacterial sphingomyelinase on the plasma membrane of host cells using a combination of Förster resonance energy transfer and expansion microscopy.

Organ and tumor dosimetry including method simplification for [Lu]Lu-PSMA-I&T for treatment of metastatic castration resistant prostate cancer.

Background: Internal dosimetry in individual patients is essential for safe and effective radioligand therapy. Multiple time point imaging for accurate dosimetry is time consuming and hence can be demanding for nuclear medicine departments as well as patients. The objectives of this study were (1) to assess absorbed doses to organs at risk and tumor lesions for [Lu]Lu-PSMA-I&T using whole body SPECT imaging and (2) to investigate possible simplified dosimetry protocols.

Small fibre neuropathy in Fabry disease: a human-derived neuronal disease model and pilot data.

Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants in the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation of globotriaosylceramide. To study the underlying pathomechanism of Fabry-associated small fibre neuropathy, we generated a neuronal disease model using patient-derived induced pluripotent stem cells from three Fabry patients and one healthy control.

Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes.

Endocytosis is a common process observed in most eukaryotic cells, although its complexity varies among different organisms. In , the endocytic machinery is under special selective pressure because rapid membrane recycling is essential for immune evasion. This unicellular parasite effectively removes host antibodies from its cell surface through hydrodynamic drag and fast endocytic internalization.

The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.

The accumulation of lipid droplets (LDs) and ceramides (Cer) is linked to non-alcoholic fatty liver disease (NAFLD), regularly co-existing with type 2 diabetes and decreased immune function. Chronic inflammation and increased disease severity in viral infections are the hallmarks of the obesity-related immunopathology. The upregulation of neutral sphingomyelinase-2 (NSM2) has shown to be associated with the pathology of obesity in tissues.

Visualizing the trans-synaptic arrangement of synaptic proteins by expansion microscopy.

High fidelity synaptic neurotransmission in the millisecond range is provided by a defined structural arrangement of synaptic proteins. At the presynapse multi-epitope scaffolding proteins are organized spatially at release sites to guarantee optimal binding of neurotransmitters at receptor clusters. The organization of pre- and postsynaptic proteins in trans-synaptic nanocolumns would thus intuitively support efficient information transfer at the synapse.

Tumor Response Evaluation Using iRECIST: Feasibility and Reliability of Manual Versus Software-Assisted Assessments.

Objectives: To compare the feasibility and reliability of manual versus software-assisted assessments of computed tomography scans according to iRECIST in patients undergoing immune-based cancer treatment.

Methods: Computed tomography scans of 30 tumor patients undergoing cancer treatment were evaluated by four independent radiologists at baseline (BL) and two follow-ups (FU), resulting in a total of 360 tumor assessments (120 each at BL/FU1/FU2). After image interpretation, tumor burden and response status were either calculated manually or semi-automatically as defined by software, respectively.

characterization of cells derived from a patient with the variant c.376A>G (p.S126G) highlights a non-pathogenic role in Fabry disease.

Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene . Variants of unknown significance (VUS) are frequently found in and challenge clinical management.

Characterization of Surface Modifications in Oxygen Plasma-Treated Teflon AF1600.

We explore the surface properties of Teflon AF1600 films treated by oxygen plasma with various procedure parameters. Contact angle (CA) measurements, scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron microscopy (XPS) are employed to investigate the wetting behavior, surface topography, and chemical composition, respectively. While the etched thickness reveals a linear relationship to the applied plasma energy, the surface presents various wetting properties and topographies depending on the plasma energy: low advancing and zero receding CA (1 kJ), super high advancing and zero receding CA (2-3 kJ), and super high advancing and high receding CA (≥4.

Multifunctional siRNA/ferrocene/cyclodextrin nanoparticles for enhanced chemodynamic cancer therapy.

The therapeutic outcome of chemodynamic therapy (CDT) is greatly hindered by the presence of oxidative damage repair proteins (MTH1) inside cancer cells. These oxidative damage repair proteins detoxify the action of radicals generated by Fenton or Fenton-like reactions. Hence, it is extremely important to develop a simple strategy for the downregulation of MTH1 protein inside cancer cells along with the delivery of metal ions into cancer cells.

Interaction of human keratinocytes and nerve fiber terminals at the neuro-cutaneous unit.

Traditionally, peripheral sensory neurons are assumed as the exclusive transducers of external stimuli. Current research moves epidermal keratinocytes into focus as sensors and transmitters of nociceptive and non-nociceptive sensations, tightly interacting with intraepidermal nerve fibers at the neuro-cutaneous unit. In animal models, epidermal cells establish close contacts and ensheath sensory neurites.

Cyclophilin A is a ligand for RAGE in thrombo-inflammation.

Aims: Cyclophilin A (CyPA) induces leucocyte recruitment and platelet activation upon release into the extracellular space. Extracellular CyPA therefore plays a critical role in immuno-inflammatory responses in tissue injury and thrombosis upon platelet activation. To date, CD147 (EMMPRIN) has been described as the primary receptor mediating extracellular effects of CyPA in platelets and leucocytes.

Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma.

The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood.

PCNA as Protein-Based Nanoruler for Sub-10 nm Fluorescence Imaging.

Super-resolution microscopy has revolutionized biological imaging enabling direct insight into cellular structures and protein arrangements with so far unmatched spatial resolution. Today, refined single-molecule localization microscopy methods achieve spatial resolutions in the one-digit nanometer range. As the race for molecular resolution fluorescence imaging with visible light continues, reliable biologically compatible reference structures will become essential to validate the resolution power.

Correction: Brosch et al. Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration. 2022, , 5794.

Philipp Kreisz was not included as an author in the original publication [...

Re-Engineered Pseudoviruses for Precise and Robust 3D Mapping of Viral Infection.

Engineered vesicular stomatitis virus (VSV) pseudotyping offers an essential method for exploring virus-cell interactions, particularly for viruses that require high biosafety levels. Although this approach has been employed effectively, the current methodologies for virus visualization and labeling can interfere with infectivity and lead to misinterpretation of results. In this study, we introduce an innovative approach combining genetic code expansion (GCE) and click chemistry with pseudotyped VSV to produce highly fluorescent and infectious pseudoviruses (clickVSVs).

Enhanced synaptic protein visualization by multicolor super-resolution expansion microscopy.

Significance: Understanding the organization of biomolecules into complexes and their dynamics is crucial for comprehending cellular functions and dysfunctions, particularly in neuronal networks connected by synapses. In the last two decades, various powerful super-resolution (SR) microscopy techniques have been developed that produced stunning images of synapses and their molecular organization. However, current SR microscopy methods do not permit multicolor fluorescence imaging with 20 to 30 nm spatial resolution.

Trifunctional Linkers Enable Improved Visualization of Actin by Expansion Microscopy.

Expansion microscopy (ExM) revolutionized the field of super-resolution microscopy by allowing for subdiffraction resolution fluorescence imaging on standard fluorescence microscopes. However, it has been found that it is hard to visualize actin filaments efficiently using ExM. To improve actin imaging, multifunctional molecules have been designed with moderate success.

Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.

Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy.

Expansion microscopy in honeybee brains for high-resolution neuroanatomical analyses in social insects.

The diffraction limit of light microscopy poses a problem that is frequently faced in structural analyses of social insect brains. With the introduction of expansion microscopy (ExM), a tool became available to overcome this limitation by isotropic physical expansion of preserved specimens. Our analyses focus on synaptic microcircuits (microglomeruli, MG) in the mushroom body (MB) of social insects, high-order brain centers for sensory integration, learning, and memory.

PSMA hybrid imaging in prostate cancer - current applications and perspectives.

Background: Prostate cancer (PCa) is the most common malignancy in men and the second most common tumor-associated cause of death in the male population in Germany. Prostate-specific membrane antigen (PSMA)-targeted hybrid imaging using positron emission tomography (PET) in combination with CT or MRI represents a comparably new method that gained increasing importance in the diagnostic process of PCa in recent years.

Method: Current applications of PSMA hybrid imaging were summarized according to the German and European guidelines on PCa.