Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes.

Whole-body cellular mapping in mouse using standard IgG antibodies.

Whole-body imaging techniques play a vital role in exploring the interplay of physiological systems in maintaining health and driving disease. We introduce wildDISCO, a new approach for whole-body immunolabeling, optical clearing and imaging in mice, circumventing the need for transgenic reporter animals or nanobody labeling and so overcoming existing technical limitations. We identified heptakis(2,6-di-O-methyl)-β-cyclodextrin as a potent enhancer of cholesterol extraction and membrane permeabilization, enabling deep, homogeneous penetration of standard antibodies without aggregation.

Toward understanding and exploiting tumor heterogeneity.

The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized.

Early stages of Golgi vesicle and tubule formation require diacylglycerol.

We have investigated the role for diacylglycerol (DAG) in membrane bud formation in the Golgi apparatus. Addition of propranolol to specifically inhibit phosphatidate phosphohydrolase (PAP), an enzyme responsible for converting phosphatidic acid into DAG, effectively prevents formation of membrane buds. The effect of PAP inhibition on Golgi membranes is rapid and occurs within 3 min.

Commuting between Golgi cisternae--mind the GAP!

Intracellular transport has remained central to cell biology now for more than 40 years. Despite this, we still lack an overall mechanistic framework that describes transport in different parts of the cell. In the secretory pathway, basic questions, such as how biosynthetic cargo traverses the pathway, are still debated.

Novel scoring function for modeling structures of oligomers of transmembrane alpha-helices.

Specific non-covalent interactions between transmembrane (TM) alpha-helices are important in a variety of biological processes. Experimental and computational studies have shown that van der Waals interactions play an important role in the tight packing between TM alpha-helices, although polar interactions can also be important in some instances. Based on the assumption that van der Waals interaction alone is sufficient for a meso-scale (residue-scale) description of the interaction between TM alpha-helices, we have designed a novel residue-scale scoring function for modeling structures of oligomers of TM alpha-helices.

Anomalous subdiffusion is a measure for cytoplasmic crowding in living cells.

Macromolecular crowding dramatically affects cellular processes such as protein folding and assembly, regulation of metabolic pathways, and condensation of DNA. Despite increased attention, we still lack a definition for how crowded a heterogeneous environment is at the molecular scale and how this manifests in basic physical phenomena like diffusion. Here, we show by means of fluorescence correlation spectroscopy and computer simulations that crowding manifests itself through the emergence of anomalous subdiffusion of cytoplasmic macromolecules.

Spatiotemporal dynamics of the COPI vesicle machinery.

Assembly of the coat protein I (COPI) vesicle coat is controlled by the small GTPase ADP ribosylation factor 1 (ARF1) and its GTPase-activating protein, ARFGAP1. Here, we investigate the diffusional behaviours of coatomer, the main component of the coat, and also those of ARF1 and ARFGAP1. Using fluorescence-correlation spectroscopy, we found that most ARF1 and ARFGAP1 molecules are highly mobile in the cytosol (diffusion constant D approximately equal to 15 microm(2) s(-1)), whereas coatomer diffuses 5-10 times more slowly than expected (D approximately equal to 1 microm(2) s(-1)).

Cisternal maturation and vesicle transport: join the band wagon! (Review).

'No cellular organelle has been the subject of as many, as long-lasting or as diverse polemics as the Golgi apparatus'. This statement was made by Whaley almost 30 years ago in the book The Golgi Apparatus and still holds true today, perhaps more then ever. Why is this? How come something as mundane as a series of intracellular membrane bound structures continues to fascinate and captivate a large section of the cell biology community? One simple reason (putting polemics aside) is that the secretory pathway appears deceptively simple.