Biology subjects

Lee, I.-J.

Publications and source records attributed to Lee, I.-J..

5 recordsLinked to original sources

bioRxiv2026

Components of an ESCRT-independent nuclear envelope assembly pathway

In many cells, the nuclear envelope (NE) must be reassembled after mitosis and holes in the nuclear membrane must be "sealed." During NE assembly, the NE-specific adaptor, Cmp7, recruits/activates ESCRT-III proteins to mediate NE sealing. However, recent evidence suggests the presence of additional mechanisms. In a screen using the fission yeast, S. japonicus, we recently implicated the ESCRT adaptor, Alx1, and a conserved, but little studied protein, Vid27, in Cmp7-independent NE assembly. Here, we provide direct evidence that Alx1 functions in a Cmp7- and ESCRT-independent NE assembly pathway via positive regulation of Vid27. Consistent with a role in membrane remodeling, Vid27 localizes to sites of postmitotic NE sealing and is essential in S. japonicus. Alx1 and Vid27 interact and mutations disrupting the predicted interaction interface abolish Alx1s enhancement of Vid27 function at the NE. These findings define components of a new Cmp7- and ESCRT-independent NE assembly pathway, advancing our understanding of mechanisms that maintain the integrity of the nucleus.

cell biology↗

bioRxiv2023

Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart

Nicotine is the primary addictive component in tobacco products. Through its actions on the heart and autonomic nervous system, nicotine exposure is associated with electrophysiological changes and increased arrhythmia susceptibility. However, the underlying mechanisms are unclear. To address this, we treated rabbits with transdermal nicotine (NIC, 21 mg/day) or control (CT) patches for 28 days prior to performing dual optical mapping of transmembrane potential (RH237) and intracellular Ca2+ (Rhod-2 AM) in isolated hearts with intact sympathetic innervation. Sympathetic nerve stimulation (SNS) was performed at the 1st - 3rd thoracic vertebrae, and {beta}-adrenergic responsiveness was additionally evaluated as changes in heart rate (HR) following norepinephrine (NE) perfusion. Baseline ex vivo HR and SNS stimulation threshold were increased in NIC vs. CT (P = 0.004 and P = 0.003 respectively). Action potential duration alternans emerged at longer pacing cycle lengths (PCL) in NIC vs. CT at baseline (P = 0.002) and during SNS (P = 0.0003), with similar results obtained for Ca2+ transient alternans. SNS reduced the PCL at which alternans emerged in CT but not NIC hearts. NIC exposed hearts also tended to have slower and reduced HR responses to NE perfusion. While fibrosis was unaltered, NIC hearts had lower sympathetic nerve density (P = 0.03) but no difference in NE content vs. CT. These results suggest both sympathetic hypo-innervation of the myocardium and diminished {beta}-adrenergic responsiveness with NIC. This autonomic remodeling may underlie the increased risk of arrhythmias associated with nicotine exposure, which may be further exacerbated with continued long-term usage. NEW & NOTEWORTHYHere we show that chronic nicotine exposure was associated with increased heart rate, lower threshold for alternans and reduced sympathetic electrophysiological responses in the intact rabbit heart. We suggest that this was due to the sympathetic hypo-innervation of the myocardium and diminished {beta}- adrenergic responsiveness observed following nicotine treatment. Though these differences did not result in increased arrhythmia propensity in our study, we hypothesize that prolonged nicotine exposure may exacerbate this pro-arrhythmic remodeling.

physiology↗

bioRxiv2022

Omicron-specific mRNA vaccine induced potent neutralizing antibody against Omicron but not other SARS-CoV-2 variants

The emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals receiving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a "Hybrid" vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specific RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.

microbiology↗

bioRxiv2019

Phytohormonal cross-talk modulate Bipolaris sorokiniana (Scc.)interaction with Zea mays

Besides acting as growth inducing molecule, Gibberellin (GA3) also confers the compatibility of microbial interactions with host. We inoculated 11 days old Z. mays seedlings grown under hydroponic conditions and high GA3 levels with Bipolaris sorokiniana (BIPOL) at the spore density (SD) of OD0.6. The high level of GA3 negatively affected the growth of the seedlings, accompanied by the high level of stress deducing secondary metabolites (proline, total flavanoids, phenylpropanoids, and glucosinolides). Moreover, high level of GA3 produced a hypersensitive response (HR) in the seedlings. The HR developed cross talks with IAA and trans-zeatins and triggered higher production of hypersensitive inducing biomolecules. The other HR co-related biological processes were demonstrated by high phytoalexins level and high protease activities. Such activities ultimately inhibited the colonization of BIPOL on the roots of maize seedlings. The products of the genes expressed at high GA3 also conferred the deterrence of BIPOL colonization at SD = OD0.6. Intriguingly, when we inhibited GA3 biosynthesis in the seedlings with aerially sprayed uniconizole, prior to BIPOL treatment, the BIPOL colonized and subsequently promoted the seedling growth. This low level of GA3 after BIPOL treatment checked the high level of secondary metabolites and hypersensitivity inducing molecules. The results, thus suggested that the aforementioned processes only happened in the BIPOL at SD (OD0.6), whereas the SD at lower levels (OD0.2 or OD0.4) neither promoted the growth of uniconizole pre-treated seedlings nor produced HR in control seedlings of maize plant.

physiology↗

bioRxiv2018

Ethylene mitigates waterlogging stress by regulating glutathione biosynthesis-related transcripts in soybeans

Waterlogging stress is a restrictive factors in soybean productivity worldwide. Plants utilize various physio-chemical changes to mitigate waterlogging stress. In current study, the regulatory roles of seven kinds of plant growth regulators, including abscisic acid (ABA), ethylene (ethephon, ETP), gibberellins (GA4), indole-3-acetic acid (IAA), kinetine (KT), jasmonic acid (JA) and salicylic acid (SA), were determined for soybeans under waterlogging conditions. Based on the results, the donor source of ethylene was selected and its role was further examined regarding physiochemical alteration and glutathione biosynthesis-related transcripts through application of exogenous ETP. ETP application mitigated waterlogging stress and significantly improved the efficiency of photosynthesis and increased bioactive GA4 contents compared to that of untreated plants. Element and amino acid contents among the treatments were significantly different. Total elements and amino acid contents were increased in 100 M ETP-treated soybean plants. ETP application induced adventitious root initiation, improved root surface area, and significantly increased glutathione transferases expression and glutathione relative to that of non-ETP treated soybean plants. Finally, 100 M-ETP application induced up-regulated protein content and glutathione s-transferase DHAR2 as compared to that of soybeans under waterlogging-conditions only. ETP could induce various biochemical and transcriptional modulations that strengthen plant growth and mitigate waterlogging stress.\n\nHighlightEthylene application to soybean plants after waterlogging up-regulates glutathione transferase genes. Higher glutathione activity, as well as increased glutathione s-transferase DHAR2 protein content was induced to scavenge reactive oxygen species.

plant biology↗