Biology subjects

Lin, P.-J.

Publications and source records attributed to Lin, P.-J..

4 recordsLinked to original sources

bioRxiv2025

Dephosphorylation of YES kinase-mediated co-chaperone DNAJB6b phosphorylation attenuates tau protein aggregation

Alzheimers disease (AD) is a neurodegenerative disorder characterized by a gradual deterioration of memory. Here, we examine the biological consequences of phosphorylation-mediated chaperone activity in AD-associated tau aggregates. Increased phosphorylation of DNAJB6b at Y53 is observed in the brain lysates of AD patients. Our research found that an activated Src family kinase, YES, phosphorylates Y53 within the J-domain of DNAJB6b and enhances the binding between DNAJB6b and Hsp70. The strengthened association between DNAJB6b and Hsp70 may lead to the accumulation of tau aggregates. These findings suggest that the up-regulation of YES kinase modifies DNAJB6b, and that the resulting alteration of DNAJB6b-dependent tau disaggregation may contribute to an increased risk of developing AD. Additionally, phosphor-DNAJB6b at Y53 may serve as a biomarker for the prognosis and diagnosis of AD.

neuroscience↗

bioRxiv2025

Hyperglycemia-Driven Hepatic Immune Dysfunction Facilitates Microbial Dissemination Post-Myocardial Infarction

BackgroundThe gut microbiome is intimately connected to cardiovascular health through the gut-heart axis and plays a pivotal role in maintaining homeostasis. Myocardial infarction (MI) disrupts this homeostatic balance, leading to widespread adverse effects. Hyperglycemia, a hallmark of metabolic dysfunction, further exacerbates these disruptions, emphasizing the need to understand the underlying mechanisms to develop effective therapeutic strategies for mitigating the cascading complications along the gut-heart axis. This study aims to elucidate the dynamics of gut barrier disruption during MI, and explore the livers function as an immune sentinel in this process, with a focus on the impact of hyperglycemia on microbial dissemination, systemic inflammation, and liver immune function. MethodsA murine MI model was used to evaluate gut permeability, bacterial translocation, and hepatic immune responses. MI was induced via permanent left anterior descending artery ligation. Hyperglycemia was established through streptozotocin injections and a high-fat, high-sugar diet. Gut barrier integrity was assessed using FITC-dextran assays, and microbial translocation was tracked through intravital imaging and anaerobic bacterial cultures from multiple organs. Hepatic immune function was analyzed via flow cytometry, cytokine profiling, and phagocytosis assays. 16S rRNA sequencing characterized the composition of translocated bacteria. ResultsMI significantly increased intestinal permeability, with hyperglycemia further exacerbating gut barrier dysfunction. Intravital imaging revealed bacterial translocation through the portal vein to the liver, highlighting the livers role in microbial interception. Hyperglycemia impaired hepatic macrophage function by activating NLRP3 inflammasome signaling, reducing bacterial clearance and promoting persistent liver colonization. Systemic inflammatory cytokines, particularly TNF-, were elevated, further facilitating microbial dissemination. 16S rRNA sequencing demonstrated host-dependent stochastic variability in translocated bacterial composition. ConclusionThe liver serves as a key immune regulator in the gut-liver-heart axis but is functionally compromised under hyperglycemia, exacerbating systemic inflammation and microbial dissemination post-MI. Targeting NLRP3 signaling and restoring gut barrier integrity may mitigate post-MI complications, particularly in hyperglycemic conditions. These findings underscore the need for integrated therapeutic strategies incorporating metabolic control and microbiome-targeted interventions to improve post-MI outcomes.

immunology↗

bioRxiv2020

Plagues of Desert Locust: No invasion risk to China

Recently, the most serious upsurge of desert locust (Schistocerca gregaria) in the last 25 years is spreading across eastern Africa and southwestern Asia. Parts of the desert locust invasion area, namely the northern border areas of Pakistan and India are very close to China, and whether locust swarms will invade China is of wide concern. To answer this question, we identified areas of potentially suitable habitat for the desert locust within China based on historical precipitation and temperature data, and found that parts of Xinjiang and Inner Mongolia provinces could provide ephemeral habitat in summer, but these places are remote from any other desert locust breeding area. Presently, the desert locust populations in Pakistan and India are mature and have laid eggs, and are less likely to spread long distances. The next generation of adults will appear in April and May, and so we examined twenty years historical wind data (2000-2019) for this period. Our results showed that winds at the height of locust swarm flight blew eastward during April and May, but the wind speeds were quite slow and would not facilitate desert locust eastward migration over large distances. Furthermore, simulated trajectories of desert locust swarms with 10 days migration mostly ended within India. The most easterly point of these trajectories just reached eastern India, close to the border between India and Myanmar, and this is very close to the eastern border of the invasion area of desert locust described in previous studies. In conclusion, the risk that the desert locust will invade China is very low.

ecology↗

bioRxiv2020

Characterization of the dimeric interactions of dimeric and tetrameric conformations of the PvNV protrusion-domain using a mixed DFT/QTAIM approach

The protrusion-domain (P-domain) of Penaeus vannamei nodavirus (PvNV) exists as two dimer-dimer conformations: one is a protein dimer and the other is a protein tetramer. We undertook a theoretical study to gain a clear understanding of the nature of the stabilizing interactions at the dimeric interfaces of the dimeric and tetrameric conformations of the PvNV P-domain (PvNVPd) using the quantum theory of atoms in molecules (QTAIM) and natural-bond orbital (NBO) analyses in the framework of the density-functional theory (DFT) approach. The QTAIM analysis characterized the presence of multiple hydrogen bonds of common types with strength ranging from electrostatic to the covalent limit inside the PvNVPd dimer-dimer interfaces. Val257-Lys335, Phe294-Val330, Gln296-Thr328, Glu296-Thr329, Thr328-Gln297, Val330-Ala293, Lys335-Asp256 and Lys335-Val257 pairs are critical residue pairs of all three dimeric interfaces of PvNVPd. They preserve these dimeric interfaces through charge-charge, charge-dipole, dipole-dipole, hydrophobic and hydrogen bond interactions. The strongest intermolecular dimer-dimer interactions belong to the dimeric interface between subunits A and B of PvNVPd in the tetrameric conformation.

biochemistry↗