Biology subjects

Lee, M.-H.

Publications and source records attributed to Lee, M.-H..

At least 19 recordsLinked to original sources

bioRxiv2026

Programmable domestication of thermophilic bacteria through removal of non-canonical defense systems

Thermophilic bacteria offer major advantages for industrial biotechnology, yet most remain genetically intractable because cellular defense systems block efficient DNA acquisition. Here, we present a programmable domestication strategy that converts wild Geobacillus strains into genetically tractable thermophilic hosts. We developed the Domestication of Non-Model Bacteria (DNMB) Suite, a multi- omics-guided computational framework that systematically identifies genetic barriers to transformation. DNMB analysis revealed that non-canonical nuclease-based defense systems, including Wadjet II, constitute dominant barriers to DNA uptake in previously intractable Geobacillus strains. Targeted deletion of these loci increased transformation efficiency by up to six orders of magnitude. We further established a hierarchical thermophilic engineering toolkit that integrates plasmid artificial modification, conjugation-assisted DNA delivery, and genome editing using an endogenous CRISPR-Cas9 system. The resulting domesticated strains support stable heterologous expression and tunable genetic control at elevated temperatures. Together, these results establish a generalizable framework for transforming genetically intractable thermophiles into programmable industrial chassis.

bioengineering↗

bioRxiv2025

A gastric microbial chromatin remodeler drives gastric cancer progression and immune evasion by reprogramming the host epigenome

Emerging evidence highlights the crucial role of microbial communities in modulating cancer development and progression. In gastric cancer (GC), we identify Streptococcus anginosus (SA) as a tumor-resident oncobacterium that drives both tumor progression and immune evasion. We define a novel mechanism in which SA secretes extracellular vesicles (saEVs) that translocate the bacterial chromatin remodeler saSNF2 into host cell. There, saSNF2 partners with host transcription factor TEAD1--through its ATPase activity and participation in BAF complex assembly--to coordinately activate oncogenic transcription. This transkingdom interaction upregulates the palmitoyltransferase ZDHHC11, which in turn stabilizes PD-L1 via palmitoylation to establish an immunosuppressive niche, while also amplifying other TEAD1 target genes to fuel tumor progression. Functionally, saEVs promote tumor growth and limit CD8+ T-cell infiltration in vivo. Strikingly, pharmacological inhibition of ZDHHC11 reverses immune evasion and synergizes with anti-PD-1 checkpoint blockade. Our results establish SA as a multifaceted driver of GC and reveal the saSNF2-ZDHHC11 axis as a promising target to potentiate immunotherapy.

cancer biology↗

bioRxiv2025

Millisecond-Scale White Matter Dynamics Underlying Visuomotor Integration

In the conventional neuropsychological model, nonverbal visuospatial processing is predominantly handled by the right hemisphere, whereas verbal processing occurs in the left, with right-hand responses governed by the left motor cortex. Using intracranial EEG and MRI tractography, we investigated the timing and white matter networks involved in processing nonverbal visuospatial stimuli, forming response decisions, and generating motor outputs. Within 200 ms of stimulus onset, we observed widespread increases in functional connectivity and bidirectional neural flows from visual to association cortices, predominantly in the right hemisphere. Engagement of the right anterior middle frontal gyrus improved response accuracy; however, the accompanying enhancement in intra-hemispheric connectivity delayed response times. In the final 100 ms before right-hand response, functional connectivity and bidirectional communication via the corpus callosum between the right and left motor cortices became prominent. These findings provide millisecond-level support for the established model of hemispheric specialization, while highlighting a trade-off between accuracy and speed governed by the right dorsolateral prefrontal network. They also underscore the critical timing of callosal transmission of response decisions formed in right-hemispheric networks to the left-hemispheric motor system. HighlightsNeural information propagates through fasciculi during a visuomotor task. Non-verbal visuospatial analysis is mediated with right-hemispheric dominance. The right middle frontal gyrus improves response accuracy but delays responses. Interhemispheric information transfer occurs immediately before motor responses. This transfer between motor cortices is mediated by the corpus callosum.

neuroscience↗

bioRxiv2025

Normative high-frequency oscillation phase-amplitude coupling and effective connectivity under sevoflurane

Resective surgery for pediatric drug-resistant focal epilepsy often requires extraoperative intracranial electroencephalography recording to accurately localize the epileptogenic zone. This procedure entails multiple neurosurgeries, intracranial electrode implantation and explantation, and days of invasive inpatient evaluation. There is a need for methods to reduce diagnostic burden and introduce objective epilepsy biomarkers. Our preliminary studies aimed to address these issues by using sevoflurane anesthesia to rapidly and reversibly activate intraoperative phase-amplitude coupling between delta and high-frequency activities, as well as high-frequency activity-based effective connectivity. Phase-amplitude coupling can serve as a proxy for spike-and-wave discharges, and effective connectivity describes the spatiotemporal dynamics of neural information flow among regions. Notably, sevoflurane activated these interictal electrocorticography biomarkers most robustly in areas whose resection led to seizure freedom. However, they were also increased in normative brain regions that did not require removal for seizure control. Before using these electrocorticography biomarkers prospectively to guide resection, we should understand their endogenous distribution and propagation pathways, at different anesthetic stages. In the current study, we highlighted the normative distribution of delta and high-frequency activity phase-amplitude coupling and effective connectivity under sevoflurane. Normative data was derived from nineteen patients, whose ages ranged from four to eighteen years and included eleven males. All achieved seizure control following focal resection. Electrocorticography was recorded at an isoflurane baseline, during stepwise increases in sevoflurane concentration, and also during extraoperative slow-wave sleep without anesthesia. Normative electrode sites were then mapped onto a standard cortical surface for anatomical visualization. Dynamic tractography traced white matter pathways that connected sites with significantly augmented biomarkers. Finally, we analyzed all sites --regardless of normal or abnormal status -- to determine whether sevoflurane-enhanced biomarker values could intraoperatively localize the epileptogenic sites. We found that normative electrocorticography biomarkers increased as a function of sevoflurane concentration, especially in bilateral frontal and parietal lobe regions (Bonferroni-corrected p-values <0.05). Callosal fibers directly connected homotopic Rolandic regions exhibiting elevated phase-amplitude coupling. The superior longitudinal fasciculus linked frontal and parietal association cortices showing augmented effective connectivity. Higher biomarker values, particularly at three to four volume percent sevoflurane, characterized epileptogenicity and seizure-onset zone status (Bonferroni-corrected p-values <0.05). Supplementary analysis showed that epileptogenic sites exhibited less augmentation in delta-based effective connectivity. This study helps clarify the normative distribution of, and plausible propagation pathways supporting, sevoflurane enhanced electrocorticographic biomarkers. Future work should confirm that sevoflurane-activated electrocorticography biomarkers can predict postoperative seizure outcomes in larger cohorts, to establish their clinical utility.

neuroscience↗

bioRxiv2025

Visualization of functional and effective connectivity underlying auditory descriptive naming

ObjectiveWe visualized functional and effective connectivity within specific white matter networks in response to auditory descriptive questions. MethodsWe investigated 40 Japanese-speaking patients with focal epilepsy and estimated connectivity measures using cortical high-gamma dynamics and MRI tractography. ResultsHearing a wh-interrogative at question onset enhanced inter-hemispheric functional connectivity, with left-to-right callosal facilitatory flows between the superior-temporal gyri, contrasted by functional connectivity diminution with right-to-left callosal suppressive flows between dorsolateral prefrontal regions. Processing verbs associated with concrete objects or adverbs increased left intra-hemispheric connectivity, with bidirectional facilitatory flows through extensive white matter pathways. Questions beginning with what, compared to where, induced greater neural engagement in the left posterior inferior-frontal gyrus at question offset, linked to enhanced functional connectivity and bidirectional facilitatory flows to the temporal lobe neocortex via the arcuate fasciculus. During overt responses, inter-hemispheric functional connectivity was enhanced, with bidirectional callosal flows between Rolandic areas, and individuals with higher IQ scores exhibited less prolonged neural engagement in the left posterior middle frontal gyrus. ConclusionsVisualization of directional neural interactions within white matter networks during overt naming is feasible. SignificancePhrase order may influence network dynamics in listeners, even when presented with auditory descriptive questions conveying similar meanings.

neuroscience↗

bioRxiv2025

Dynamic Causal Tractography Analysis of Auditory Descriptive Naming:An Intracranial Study of 106 Patients

Humans understand and respond to spoken questions through coordinated activity across distributed cortical networks. However, the causal roles of connectivity engagements alternating across multiple white matter bundles remain understudied at the whole-brain scale. Using intracranial high-gamma activity recorded from 7,792 non-epileptic electrode sites in 106 epilepsy patients who underwent direct cortical stimulation mapping, we constructed an atlas visualizing the millisecond-scale dynamics of functional connectivity during a naming task in response to auditory questions. This atlas, the Dynamic Causal Tractography Atlas, identified functional connectivity patterns at specific time windows most strongly associated with stimulation-induced language- and speech-related manifestations (p-value range: 2.5 x 10-5 to 6.6 x 10-14; rho range: +0.54 to +0.82). The atlas revealed that no single intra-hemispheric fasciculus was consistently engaged in all naming stages; instead, each fasciculus supported specific stages, with multiple distinct major fasciculi simultaneously contributing to each stage. Additionally, this atlas identified the specific linguistic stages and fasciculi where handedness effects became evident. Our findings clarify the dynamics and causal roles of alternating, coordinated neural activity through specific fasciculi during auditory descriptive naming, advancing current neurobiological models of speech network organization. Additionally, we have made our white matter streamline template and intracranial EEG data available as open-source material, enabling investigators to construct personalized dynamic tractography atlases.

neuroscience↗

bioRxiv2024

Epstein-Barr viral product-containing exosome facilitates LIF-associated immunosuppressive polarization of macrophage in nasopharyngeal carcinoma

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is characterized by a highly infiltrated, yet immunosuppressive, tumor microenvironment (TME) in which tumor-associated macrophages (TAMs) play a central role in tumor progression. In this study, we identified exosome-mediated delivery of the EBV oncoprotein LMP1, which acts via induction of leukemia inhibitory factor (LIF), as a key mechanism driving immunosuppressive macrophage polarization. Immunohistochemistry revealed that, in addition to tumor cells, LIF is primarily expressed by stromal TAMs and correlates with poor prognosis. We demonstrated that LMP1-containing exosomes are internalized by macrophages, leading to NF-{kappa}B-dependent upregulation of LIF and polarization toward an immunosuppressive M2d-like phenotype. These macrophages exhibit impaired anti-tumor activity and promote tumor proliferation and vascular dissemination in a LIF-dependent manner. Single-cell transcriptomic analyses of exosome-treated NPC biopsies revealed transcriptional reprogramming across tumor, myeloid, and lymphoid compartments impacting epithelial-mesenchymal transition (EMT); extracellular matrix (ECM) remodeling in tumor cells; immunosuppressive signaling (e.g., CD163 anti-inflammatory and VEGF signaling in macrophages); and enrichment of immune checkpoints and pathways, including PD-1, TGF{beta}-SMAD, and NF-{kappa}B-associated pathways in T cells. Exosome treatment increased expansion of CCL18+-TAMs and expression of CTLA4 in regulatory T cells and exhausted T cells. Immunohistochemistry further confirmed a positive correlation between expression of LIF and CTLA4 in NPC tumors and an inverse correlation between LIF and GZMB/CD8A. These findings define an exosome-driven LMP1-LIF axis that orchestrates immune suppression in NPC and suggest potential targets for restoring anti-tumor immunity.

cancer biology↗

bioRxiv2024

The N-degron pathway governs autophagy to promote thermotolerance in Arabidopsis

Autophagy is a vital process that enables plants to adapt to various environmental changes. During heat stress (HS), misfolded and denatured proteins accumulate in cells, necessitating autophagy for their removal. Here, we show that a core autophagy component ATG8a is targeted for degradation via the Arg/N-degron pathway. ATG8a is expressed as two alternatively spliced transcripts encoding ATG8a isoforms, namely ATG8a(S) and ATG8a(L), with distinct N-termini. While ATG8a(S) remains stable, ATG8a(L) is N-terminally processed to expose the Arg/N-degron, leading to its degradation. UBR7, identified as an N-recognin, is responsible for ubiquitination and proteasomal degradation of ATG8a(L). Notably, ATG8a(S) and ATG8a(L) show dynamic expression patterns, fluctuating ATG8a levels during the HS and recovery periods. Our findings highlight the crucial role of ATG8a turnover in conferring thermotolerance, which is governed by Arg/N-degron-mediated regulation. Understanding the molecular basis of ATG8a stability will provide valuable insights into plant resilience to HS under changing climatic conditions.

plant biology↗

bioRxiv2023

Precision-engineered biomimetics: the human fallopian tube

The fallopian tube has an essential role in several physiological and pathological processes from pregnancy to ovarian cancer. However, there are no biologically relevant models to study its pathophysiology. The state-of-the-art organoid model has been compared to two-dimensional tissue sections and molecularly assessed providing only cursory analyses of the models accuracy. We developed a novel multi-compartment organoid model of the human fallopian tube that was meticulously tuned to reflect the compartmentalization and heterogeneity of the tissues composition. We validated this organoids molecular expression patterns, cilia-driven transport function, and structural accuracy through a highly iterative platform wherein organoids are compared to a three-dimensional, single-cell resolution reference map of a healthy, transplantation-quality human fallopian tube. This organoid model was precision-engineered to match the human microanatomy. One sentence summaryTunable organoid modeling and CODA architectural quantification in tandem help design a tissue-validated organoid model.

bioengineering↗

bioRxiv2022

Non-Invasive Cancer Detection in Canine Urine through C. elegans Chemotaxis

Cancer is the leading cause of death of companion animals, and successful early treatment has been a challenge in the veterinary field. We have developed the Non-Invasive Cancer Screening (N.C.S.) Study to perform cancer detection through the analysis of canine urine samples. The test makes use of the strong olfactory system of the nematode C. elegans, which was previously shown to positively respond to urine samples from human cancer patients. We performed a proof-of-concept study to optimize the detection capability in urine samples obtained from dogs with naturally occurring cancers. In this study, we established a scale for identifying the cancer risk based on the magnitude of the chemotaxis index of C. elegans towards a canine urine sample. Through validation, the N.C.S. Study achieved a sensitivity of 85%, showing that it is highly sensitive to indicating the presence of cancer across multiple types of common canine cancers. The test also showed a 93% specificity to cancer samples, indicating a low rate of over-identifying cancer risk. From these results, we have demonstrated the ability to perform low-cost, non-invasive cancer detection in companion animals, a method which can increase the ability to perform cancer diagnosis and treatment.

cancer biology↗

bioRxiv2022

Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection - without neuroinvasion - and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

neuroscience↗

bioRxiv2021

Comparative genomics of three Colletotrichum scovillei strains and genetic analysis revealed genes involved in fungal growth and virulence on chili pepper

Colletotrichum scovillei is a virulent pathogen and the dominant species causing anthracnose of chili pepper in many Asian countries. Three strains of this pathogen, Coll-524, Coll-153 and Coll-365, show varied virulence on chili pepper fruit. Among the three strains, Coll-365 showed significant defects in growth and virulence. To decipher the genetic variations among these strains and identify genes contributing to growth and virulence, in this study, comparative genomic analysis and gene transformation to verify gene function were applied. The genomes of the three strains were sequenced and Coll-524 had 1.3% and 1.5% more genes than Coll-153 and Coll-365, respectively. Compared to Coll-524 and Coll-153, Coll-365 had numerous gene losses including 33 effector genes that are distributed in different scaffolds and a cluster of 14 genes in a 34-kb genomic fragment. Through gene transformation, three genes in the 34-kb fragment were identified to have functions in growth and/or virulence of C. scovillei. Gene 15019 encoding a protein related to phospholipase A2-activating protein enhanced the growth of Coll-365. A combination of 15019 with one transcription factor gene 15022 and one C6 zinc finger domain-containing protein gene 15029 was found to enhance the pathogenicity of Coll-365. Introduction of gene 15215, which encodes a LysM domain-containing protein, into Coll-365 caused a reduction in the germination rate of Coll-365. In conclusion, the higher virulent strain Coll-524 had more genes and encoded more pathogenicity related proteins and transposable elements than the other two strains, which may contribute to the high virulence of Coll-524. In addition, the absence of the 34-kb fragment plays a critical role in the defects of growth and virulence of strain Coll-365. Author SummaryColletotrichum scovillei is a highly virulent and dominant pathogen causing anthracnose of chili that leads to significant economic loss in chili production in many Asia countries. In this study we focus on finding the gene differences of three C. scovillei strains with different pathogenicity in chili pepper infection and verifying the function of some genes in the lowest virulence strain. We sequenced them and did gene annotation and genome comparison. We setup a simple mathematical method to identify gene variations between strong and weak virulence strains. Our results show that the lowest virulence strain has less pathogenicity-related genes. We also found that the absence of 14 genes in a compact genomic fragment was part of the reason of growth and virulence defect of the lowest virulence strain. We identified four genes that play roles on fungal growth and/or virulence on chili pepper. We also found a group of effector genes that specifically appear in species collected form infected chili in C. acutatum species complex. Our research provides detailed information for why the three strains have different virulence on chili pepper.

genomics↗

bioRxiv2021

The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants. HighlightsO_LICT-P59 exerts the antiviral effect on authentic Delta, Epsilon and Kappa variants in cell-based experiments. C_LIO_LICT-P59 showed neutralizing potency against variants including Delta, Epsilon, Kappa, L452R, T478K and P681H pseudovirus variants. C_LIO_LIThe administration of clinically relevant dose of CT-P59 showed in vivo C_LIO_LIprotection against Delta variants in animal challenge experiment. C_LI

microbiology↗

bioRxiv2021

Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2

P.1. or gamma variant also known as the Brazil variant, is one of the variants of concern (VOC) which appears to have high transmissibility and mortality. To explore the potency of the CT-P59 monoclonal antibody against P.1 variant, we tried to conduct binding affinity, in vitro neutralization, and in vivo animal tests. In in vitro assays revealed that CT-P59 is able to neutralize P.1 variant in spite of reduction in its binding affinity against a RBD (receptor binding domain) mutant protein including K417T/E484K/N501Y and neutralizing activity against P.1 pseudoviruses and live viruses. In contrast, in vivo hACE2 (human angiotensin-converting enzyme 2)-expressing TG (transgenic) mouse challenge experiment demonstrated that a clinically relevant or lower dosages of CT-P59 is capable of lowering viral loads in the respiratory tract and alleviates symptoms such as body weight losses and survival rates. Therefore, a clinical dosage of CT-P59 could compensate for reduced in vitro antiviral activity in P.1-infected mice, implying that CT-P59 has therapeutic potency for COVID-19 patients infected with P.1 variant. HighlightsO_LICT-P59 could bind to and neutralize P.1 variant, but CT-P59 showed reduced susceptibility in in vitro tests. C_LIO_LIThe clinical dosage of CT-P59 demonstrated in vivo therapeutic potency against P.1 variants in hACE2-expressing mice challenge study. C_LIO_LICT-P59 ameliorates their body weight loss and prevents the lethality in P.1 variant-infected mice. C_LI

microbiology↗

bioRxiv2021

Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation

The fallopian tube fimbrial epithelium (FTE), which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma (HGSC). Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of FTE. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor-thrombin-HGFA-HGF cleavage cascade confers a sustained transformation activity to FTE, HGSC. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/448625v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@13d26d3org.highwire.dtl.DTLVardef@1c00c35org.highwire.dtl.DTLVardef@1619373org.highwire.dtl.DTLVardef@117a24d_HPS_FORMAT_FIGEXP M_FIG C_FIG The fluid content of the ovulating ovarian follicle (follicular fluid [FF]) exerts a long-lasting transformation effect that is sustained after mixing with peritoneal fluid (PF). The coagulation protease cascade and hepatocyte growth factor (HGF) are responsible for the sustained activity. The high abundance of cascade proteins and pro-form HGF activator and HGF in FF/PF supports the constant supply of active-form HGF lasting for a whole month, covering the entire ovulation cycle. This sustained HGF activity promotes the proliferative repair of the ovarian surface and fallopian tube fimbrial epithelia as well as the growth of the corpus luteum. The same activity also inadvertently promotes the malignant transformation of the fimbrial epithelium, high-grade serous carcinoma, and epithelial ovarian cancer. In addition to the peritoneal cavity, ovulation sources HGF to blood circulation, which may serve an endocrine role. HIGHLIGHTO_LIOvulatory follicular fluid (FF) exerts a long-lasting transformation activity covering throughout the ovulation cycle. C_LIO_LIThe ovulation injury-coagulation proteases-hepatocyte growth factor (HGF) cascade is responsible for the sustained activity. C_LIO_LIOvulation sources HGF into the peritoneal cavity, then into the blood circulation. C_LIO_LIThis coagulation-HGF cascade promotes the transformation of fallopian tube epithelial cells and ovarian cancer cells. C_LIO_LIPhysiologically, it promotes the growth of the corpus luteum and injured epithelium after ovulation. C_LI

cancer biology↗

bioRxiv2021

Naming-related spectral responses predict neuropsychological outcome after epilepsy surgery

This prospective study determined the utility of intracranially-recorded spectral responses during naming tasks in predicting neuropsychological performance following epilepsy surgery. We recruited 65 patients with drug-resistant focal epilepsy who underwent preoperative neuropsychological assessment and intracranial EEG (iEEG) recording. The Clinical Evaluation of Language Fundamentals (CELF) evaluated the baseline and postoperative language function. During extraoperative iEEG recording, we assigned patients to undergo auditory and picture naming tasks. Time-frequency analysis determined the spatiotemporal characteristics of naming-related amplitude modulations, including high gamma augmentation (HGA) at 70-110 Hz. We surgically removed the presumed epileptogenic zone based on the extent of iEEG and MRI abnormalities while maximally preserving the eloquent areas defined by electrical stimulation mapping (ESM). The multivariate regression model incorporating auditory naming-related HGA predicted the postoperative changes in Core Language Score (CLS) on CELF with r2 of 0.37 (p = 0.015) and in Expressive Language Index (ELI) with r2 of 0.32 (p = 0.047). Independently of the effects of epilepsy and neuroimaging profiles, higher HGA at the resected language-dominant hemispheric area predicted a more severe postoperative decline in CLS (p = 0.004) and ELI (p = 0.012). Conversely, the model incorporating picture naming-related HGA predicted the change in Receptive Language Index (RLI) with r2 of 0.50 (p < 0.001). Higher HGA independently predicted a more severe postoperative decline in RLI (p = 0.03). Ancillary regression analysis indicated that naming-related low gamma augmentation as well as alpha/beta attenuation likewise independently predicted a more severe CLS decline. The machine learning-based prediction model, referred to as the boosted tree ensemble model, suggested that naming-related HGA, among all spectral responses utilized as predictors, most strongly contributed to the improved prediction of patients showing a >5-point CLS decline (reflecting the lower 25 percentile among patients). We generated the model-based atlas visualizing sites, which, if resected, would lead to such a CLS decline. The auditory naming-based model predicted patients who developed the CLS decline with an accuracy of 0.80. The model indicated that virtual resection of an ESM-defined language site would have increased the relative risk of the CLS decline by 5.28 (95%CI: 3.47 to 8.02). Especially, that of an ESM-defined receptive language site would have maximized it to 15.90 (95%CI: 9.59-26.33). In summary, naming-related spectral responses predict objectively-measured neuropsychological outcome after epilepsy surgery. We have provided our prediction model as an open-source material, which will indicate the postoperative language function of future patients and facilitate external validation at tertiary epilepsy centers.

neuroscience↗

bioRxiv2021

Target Capture Sequencing of SARS-CoV-2 Genomes Using the ONETest Coronaviruses Plus

BackgroundGenomic sequencing is important to track and monitor genetic changes in SARS-CoV-2. We introduce a target capture next-generation sequencing methodology, the ONETest Coronaviruses Plus, to sequence SARS-CoV-2 genomes and select genes of other respiratory viruses simultaneously. MethodsWe applied the ONETest on 70 respiratory samples (collected in Florida, USA between May and July, 2020), in which SARS-CoV-2 had been detected by a qualitative PCR assay. For 48 (69%) of the samples, we also applied the ARTIC protocol for Illumina sequencing. All the libraries were sequenced as 2x150 nucleotide reads on an Illumina instrument. The ONETest data were analyzed using an in-house pipeline and the ARTIC data using a published pipeline to produce consensus SARS-CoV-2 genome sequences, to which lineages were assigned using pangolin. ResultsOf the 70 ONETest libraries, 45 (64%) had a complete or near-complete SARS-CoV-2 genome sequence (> 29,000 bases and with > 90% of its bases covered by at least 10 reads). Of the 48 ARTIC libraries, 25 (52%) had a complete or near-complete SARS-CoV-2 genome sequence. In 24 out of 34 (71%) samples in which both the ONETest and ARTIC sequences were complete or near-complete and in which lineage could be assigned to both the ONETest and ARTIC sequences, the SARS-CoV-2 lineage identified was the same. ConclusionsThe ONETest can be used to sequence the SARS-CoV-2 genomes in archived samples and thereby enable detection of circulating and emerging SARS-CoV-2 variants. Target capture approaches, such as the ONETest, are less prone to loss of sequence coverage probably due to amplicon dropouts encountered in amplicon approaches, such as ARTIC. With its added value of characterizing other major respiratory pathogens, although not assessed in this study, the ONETest can help to better understand the epidemiology of infectious respiratory disease in the post COVID-19 era.

genomics↗

bioRxiv2021

The Arabidopsis ORA59 coordinates jasmonic acid- and ethylene-responsive gene expression to regulate plant immunity

Jasmonic acid (JA) and ethylene (ET) signaling modulate plant defense against necrotrophic pathogens. These hormone pathways lead to transcriptional reprogramming, which is a major part of plant immunity and requires the roles of transcription factors. ET response factors are responsible for the transcriptional regulation of JA/ET-responsive defense genes, among which ORA59 functions as a key regulator of this process and has been implicated in the JA-ET crosstalk. Here, we identified the ERELEE4 as an ORA59-binding cis-element, in addition to the well-characterized GCC box, demonstrating that ORA59 regulates JA/ET-responsive genes through direct binding to these elements in the gene promoters. Notably, ORA59 exhibited differential preference for the GCC box and ERELEE4, depending on whether ORA59 activation is achieved by JA and ET, respectively. Our results provide insights into how ORA59 can generate specific patterns of gene expression dynamics through JA and ET hormone pathways.

plant biology↗