Biology subjects

Paudel, P.

Publications and source records attributed to Paudel, P..

4 recordsLinked to original sources

bioRxiv2025

Large sharp-wave ripples promote hippocampo-cortical memory reactivation and consolidation

During sleep, ensemble activity patterns encoding recent experiences are reactivated in the hippocampus and cortex. This reactivation is coordinated by hippocampal sharp-wave ripples (SWRs) and is believed to support the early stages of memory consolidation. However, only a minority of sleep SWRs are associated with memory reactivation in the hippocampus and its downstream areas. Whether that subset of SWRs have specific physiological characteristics and directly contribute to memory performance is not known. We identified a specific subset of large SWRs linked to memory reactivation in both the hippocampus and prefrontal cortex (PFC) of mice, and found that their occurrence selectively increased during sleep following new learning. Closed-loop optogenetic SWR boosting during sleep was sufficient to enhance ensemble memory reactivation in hippocampus and PFC. This manipulation also improved subsequent memory retrieval and hippocampal-PFC coordination during waking, causally linking both phenomena to SWR-associated ensemble reactivation during sleep.

neuroscience↗

bioRxiv2021

Molecular dynamics analysis of fast-spreading severe acute respiratory syndrome coronavirus 2 variants and their effects in the interaction with human angiotensin-converting enzyme 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the Spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures to contain the spread of the disease in many countries has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread and whether they can cause a more severe disease remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (KD) values using surface plasmon resonance (SPR) assays of three fastspreading SARS-CoV-2 variants, Alpha, Beta and Gamma ones, as well as genetic factors in the host cells that may be related to the viral infection. Our results suggest that the SARS-CoV-2 variants facilitate their entry into the host cell by moderately increased binding affinities to the human ACE2 receptor, different torsions in hACE2 mediated by RBD variants, and an increased Spike exposure time to proteolytic enzymes. We also found that other host cell aspects, such as gene and isoform expression of key genes for the infection (ACE2, FURIN and TMPRSS2), may have few contributions to the SARS-CoV-2 variants infectivity. In summary, we concluded that a combination of viral and host cell factors allows SARS-CoV-2 variants to increase their abilities to spread faster than wild-type. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

molecular biology↗

bioRxiv2020

Sapphire Nanopores for Low-Noise DNA Sensing

Silicon-supported (SiS) solid-state nanopores have broad applications in single-molecule biosensing and diagnostics, but their high capacitive noise has seriously limited both their sensing accuracy and recording speed. Nanopores on insulating glass have demonstrated reduced capacitance and noise, but it remains challenging to bulk-etch amorphous glass to create membranes reproducibly and uniformly. Here a new approach is reported to form triangular sapphire-supported (SaS) nanopore membranes by batch-processing-compatible anisotropic wet etching of sapphire, with membrane dimension demonstrated from ~200 μm to 5 μm. A SaS nanopore in 68 μm-wide silicon nitride membrane has 130 times smaller capacitance (10 pF) compared to a SiS nanopore (~4 μm SiN membrane, ~1.3 nF), despite a 100 times larger membrane. It has a current noise of 18 pA over 100 kHz bandwidth, much smaller than that from our SiS nanopore (46 pA) and comparable with the best reported low-noise nanopores. Further, the SaS nanopore displays a higher signal-to-noise ratio (SNR, 21 versus 11 for SiS nanopore) in DNA sensing, although the SNR can be further improved using thinner membranes and smaller pores. The SaS nanopore presents a simple platform in both fabrication and structure that is particularly suitable for low-noise and high-speed molecular diagnostics.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2017

The structure of SALM5 suggests a dimeric assembly for the presynaptic RPTP ligand recognition

Synaptic adhesion molecules play a crucial role in the regulation of synapse development and maintenance. Recently several families of leucine rich repeat domain containing neuronal adhesion molecules have been characterized, including netrin G-ligands, LRRTMs, and the SALM family proteins. Most of these are expressed at the excitatory glutamatergic synapses, and dysfunctions of these genes are genetically linked with cognitive disorders, such as autism spectrum disorders and schizophrenia. The SALM family proteins SALM3 and SALM5, similar to SLITRKs, have been shown to bind to the presynaptic receptor protein tyrosine phosphatase (RPTP) family ligands. Here we present the 3 [A] crystal structure of the SALM5 LRR-Ig domain construct, and biophysical studies that verify the crystallographic results. We show that both SALM3 and SALM5 extracellular domains form similar dimeric structures, in which the LRR domains form the dimer interface. Both proteins bind to the RPTP lg-domains with micromolar affinity. SALM3 shows a clear preference for RPTP-ligands with the meB splice insert. This is in accordance with previous results showing that the LRR domain is also required for the ligand binding. Our structural studies and sequence conservation analysis suggests a ligand binding site and mechanism for RPTP binding via the dimeric LRR domain region.

biochemistry↗