BPS2025 - Lipidomic and structural investigation of nanodisc reconstituted membrane proteins

Biophysical Journal · 2025-02-01

Author response for "Acoustic Probing of New Biomarkers for Rapid Sickle Cell Disease Screening"

2025-07-30

Facilitation of Ca _V 3.2 channel gating in pain pathways reveals a novel mechanism of serum-induced hyperalgesia

bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-03 · 1 citations

Abstract The Ca V 3.2 isoform of T-type voltage-gated calcium channels plays a crucial role in regulating the excitability of nociceptive neurons; the endogenous molecules that modulate its activity, however, remain poorly understood. Here, we used serum proteomics and patch-clamp physiology to discover a novel peptide albumin (1-26) that facilitates channel gating by chelating trace metals that tonically inhibit Ca V 3.2 via H191 residue. Importantly, serum also potently modulated T-currents in human and rodent dorsal root ganglion (DRG) neurons. In vivo pain studies revealed that injections of serum and albumin (1-26) peptide resulted in robust mechanical and heat hypersensitivity. This hypersensitivity was abolished with a T-channel inhibitor, in Ca V 3.2 null mice and in Ca V 3.2 H191Q knock-in mice. The discovery of endogenous chelators of trace metals in the serum deepens our understanding of the role of Ca V 3.2 channels in neuronal hyperexcitability and may facilitate the design of novel analgesics with unique mechanisms of action.

Chemical Synthesis Reveals Pathogenic Role of <i>N</i>-Glycosylation in Microtubule-Associated Protein Tau

Journal of the American Chemical Society · 2025-02-17 · 17 citations

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of tau protein aggregates. In this study, we investigated the effects of N-glycosylation on tau, focusing on its impact on aggregation and phase behavior. We chemically prepared homogeneous glycoproteins with high-mannose glycans or a single N-acetylglucosamine at the confirmed glycosylation sites in K18 and 2N4R tau. Our findings reveal that N-glycosylation significantly alters biophysical properties and potentially cellular functions of tau. Small glycans promote tau aggregation and liquid–liquid phase separation (LLPS), while larger glycans reduce these effects. High mannose glycans at N410 enhance phosphorylation by GSK3β, suggesting a pathological role in AD. Functional assays demonstrate that N-glycosylation does not impact microtubule polymerization dynamics but modulates aggregation kinetics and morphology. This research underscores the importance of glycosylation in tau pathology and opens new avenues for therapeutic interventions targeting glycan processing.

A Plug and Play Flash and Freeze System for cryoTREM: Design, Build, Testing and Initial Implementation

Structural Dynamics · 2025-03-01

CryoEM increasingly attempts to incorporate time-resolved techniques to bridge the gap between static images and dynamic processes. Here we describe simple LED-based photo-flash system designed to simplify sample preparation for cryogenic sample time-resolved electron microscopy (cryoTREM). This user-friendly system offers flexibility in its operation, is cost-effective, and achieves uniform light exposure with minimal heat impact on the samples before plunge freezing. We describe the mechanical, electronic and optical components, that are tailored for easy plug and play operation for both the TFS Vitrobot and Leica GP2 plunge freezers. We will also present some initial results using this system to study a number of dynamic systems.

BPS2025 - Time-resolved cryo-EM of lipid-linked sugar transfer

Biophysical Journal · 2025-02-01

BPS2025 - Time-resolved cryo-EM of lipid-linked sugar transfer

Biophysical Journal · 2025-02-01

Author Correction: Structure and topography of the synaptic V-ATPase–synaptophysin complex

Nature · 2025-05-22

Evolution of graphene nanoflake size and morphology in atmospheric pressure microwave plasma

Journal of Vacuum Science & Technology B Nanotechnology and Microelectronics Materials Processing Measurement and Phenomena · 2025-07-01 · 2 citations

Graphenelike carbon was synthesized using an atmospheric pressure microwave plasma system, employing argon/nitrogen mixtures as carrier gases and methane as the carbon precursor. This study investigates the effects of varying methane flow rates and plasma power on carbon synthesis and final morphology. The process involves the decomposition and subsequent reorganization of carbon radicals into graphene sheets and graphitic nodules. Tungsten carbide rods with attached copper collection grids were strategically positioned at three distinct points along the plasma column to collect the synthesized carbon. The variations in particle diameter were systematically analyzed using scanning electron microscopy (SEM). Results indicate that particle diameter generally increases along the plasma column, influenced heavily by plasma length. Beyond the bulk-incandescent plasma boundary, the diameter distributions remain relatively constant, suggesting that the majority of the growth occurs in the bulk and incandescent regions. Further, an increase in methane flow rate correspondingly worsened the material quality and increased the mean particle diameter across all ports, attributed to higher carbon concentrations and lower gas temperature in the plasma. Conversely, an increase in plasma power resulted in better material quality and a decrease in particle diameter at each port, which can be attributed to the rise in gas and electron temperatures increasing favorable reaction rates. Higher thermal energy accelerates the kinetic activity of carbon species in the plasma, leading to increased fragmentation of carbon precursors. This elevated energy prevents the stable aggregation of larger graphene flakes, as higher temperatures destabilize larger particle assemblies, favoring the formation of smaller graphene structures due to enhanced atomic mobility and radical-driven fragmentation. These findings demonstrate that manipulating methane flow rates and plasma power can significantly influence carbonaceous particle size, allowing for the optimization of growth conditions to achieve industry-grade graphene. This study provides a deeper understanding of the thermodynamic and chemical mechanisms governing graphene synthesis in microwave plasma systems, offering a pathway to tailored graphene production for advanced material applications.

Acoustic probing of new biomarkers for rapid sickle cell disease screening

Lab on a Chip · 2025-12-12

Sickle cell disease (SCD) remains a critical global health issue, with high child mortality in low-resource regions. Early diagnosis is essential for improving health outcomes, but conventional diagnostic methods are unsuitable for widespread use due to the high costs of laboratory equipment. There is an urgent need for portable, cost-effective, and user-friendly point-of-care diagnostic tools that can quickly assess blood health. Here, we explore two new biomarkers enabled by acoustic probing for rapid SCD diagnosis: cell membrane stability from measuring red blood cell (RBC) lysis temperature in whole blood, and plasma protein concentration from measuring relative protein precipitation in blood plasma. Both biomarkers effectively differentiate healthy HbAA samples from pre-/no transfusion HbSS samples with high accuracy. Additionally, the RBC lysis biomarker can distinguish post-transfusion exchange HbSS samples with a lower percentage of sickled cells, indicating the potential to diagnose milder forms of SCD as well as sickle cell trait.