The yeast SUC2 gene, cloned on a multicopy plasmid pRB58, was used to study the effect of oxygen on the invertase expression of the recombinant Saccharomyces cerevisiae. Glucose repression was not the only factor affecting the invertase expression. The results obtained from the single-stage continuous cultures under microaerobic conditions showed that invertase expression was also strongly dependent on oxygen availability, and moving from anaerobic to aerobic conditions led to a five-fold increase in specific invertase activity. However, the cell yields under anaerobic conditions were quite low compared to those under aerobic conditions. These opposite effects of oxygen on cell growth and gene expression offer a strategy for maximizing invertase productivity by a two-stage continuous culture. The first stage was operated at a low level of glucose, around 100 mg/l, under aerobic conditions in order to obtain a high yield of yeast biomass, and the second stage maintained anaerobic conditions with residual glucose levels of 50 mg/l to derepress and fully induce invertase expression. The two-stage continuous culture resulted in a 2.5-fold increase in invertase productivity over that of a single-stage continuous culture.
Funding Acknowledgements Type of funding sources: None. Introduction Atrial fibrillation catheter ablation (AFCA) improves sinus node function and may defer a permanent pacemaker (PPM) implantation. We explored the clinical and genetic characteristics of the patients with AF and sinus node dysfunction (SND) who eventually needed PPM implantation after AFCA. Methods Among 2,732 AF patients with genome-wide association study (GWAS, PMRA, Thermofisher scientific, MA, USA) data who underwent the first AFCA, 244 patients (65.0, IQR [59.0, 72.0] years, male 58.2%, paroxysmal AF 79.5%) had underlying SND before AFCA (class I indication for PPM). We retrospectively investigated clinical factors, single-nucleotide polymorphisms (SNPs), and their polygenic risk score (PRS) associated with PPM-AFCA. We defined the cut-off of PRS using the Youden index. Results During median 37.9 (IQR 20.3-77.9) months follow-up, 36 out of 244 patients (16.1%) with underlying SND eventually underwent PPM implantation after AFCA (PPM-AFCA). PPM-AFCA group a had a higher body mass index (p=0.013) and large left atrial (LA) dimension (p=0.006) than their counterpart. Among 44 SNPs related to AF and SND, the rs3922844 (p=0.003) near SCN5A and rs9320841 (p=0.011) and rs1015451 (p=0.046) near CJA1 were significantly associated with PPM-AFCA. The rate of PPM-AFCA implantation was significantly higher in the high PRS group (≥1.175, 25.6%) compared to the low PRS group (<1.175, 9.38%, p=0.002, Log-rank p=0.002). LA dimension (adjusted HR 1.06, 95% CI [1.00-1.13], p=0.044) and PRS (adjusted HR 2.69, 95% CI [1.68-4.31], p<0.001) were associated with a higher risk for PPM-AFCA after adjusting clinical factors including age, sex, AF type, beta blocker, and antiarrhythmic drugs after AFCA. Conclusions In AF patients with SND, 16% with the genetic background of SCN5A and CJA1 or large atrium eventually needed PPM implantation after AFCA.
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health and Welfare the Basic Science Research Program run by the National Research Foundation of Korea (NRF). Background Atrial fibrillation (AF) is a chronic progressive disease that recurs continuously even after successful AF catheter ablation (AFCA). Objective We explored the mechanism of this long-term recurrence by comparing the patient characteristics and redo-ablation findings. Methods Among 4,248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at single centers, we enrolled 1,417 patients (71.7% male, age 60.0 [52.0–67.0] years, 57.9% paroxysmal AF) who experienced clinical recurrences (CRs) of the disease, and divided them according to the period of recurrence: within one year (n=645), 1–2 years (n=339), 2–5 years (n=308), and after 5-years (CR>5yr, n=125). We also compared the redo-mapping and ablation outcomes in 198 patients. Results In patients with a CR>5yr, the proportion of paroxysmal AF was higher (p=0.031); however, the left atrial (LA) volume (computed tomography, p=0.003), LA voltage (p=0.003), frequency of early recurrence (p<0.001), and use of post-procedure anti-arrhythmic drugs (p<0.001) were lower. A CR>5yr was independently associated with the low LA volume (odds ratio [OR] 0.99 [0.99–1.00], p=0.019), low LA voltage (OR 0.62 [0.41–0.95], p=0.030), and lower early recurrence (OR 0.39 [0.23–0.64], p<0.001). Extra-pulmonary vein (PV) triggers (P for trend 0.003) during repeat procedures were significantly greater in patients with a CR>5yr, despite no difference in the de novo protocol. The rhythm outcome of repeat ablation procedures did not differ with the timing of the CR (log-rank p=0.330). Conclusions Patients with a later CR showed a smaller LA volume, lower LA voltage, and higher extra-PV triggers during the repeat procedure, suggesting progression of AF.
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): a grant [2022R1I1A1A0106342211] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) which is funded by the Ministry of Science, ICT & Future Planning (MSIP) Background It has been suggested that the high dominant frequency (DF) site plays an atrial fibrillation (AF) driver, but its relationship with the atrial substrate voltage map (Vm) in the entire chamber AF map has yet to be studied. We explored the relationship between the DF site during AF and Vm in the entire chamber maps by applying the human left atrial (LA) electroanatomical map (EAM) to the digital twin AF map. Methods We acquired LA substrate Vm (at sinus rhythm, >800 points bipolar electrograms) of 110 patients with persistent AF (male 72.7%, 58.7±9.8 years old) who underwent AF catheter ablation. We applied EAM to digital twins (0.4 million nodes), reflecting anatomy, histology, and electrophysiology. We evaluated the highest 10% DF areas for 6 sec after inducing virtual AF. The correlation between the highest 10% DF and the low Vm areas (<0.2mV) was evaluated in the LA region of 10 segments. Results The mean voltage of the entire LA area was 1.96±0.85 mV (2.19±0.82 mV extra-PV area, 1.33±0.93 mV PV area) in 110 patients. The correlation between low Vm and high DF areas was not significant in the entire LA (r=0.106, p<0.001), extra-PV (r=0.157, p<0.001), and PV (r=0.079, p=0.097) areas. In the LA 10 segment regional analysis, 72 patients (65.5%) showed the co-localization of the highest DF in the region with the lowest Vm, and 14 patients (12.7%) had the lowest Vm segment in the region with the highest DF. The mean voltage where high DF appeared was 0.69±1.35 mV, and the mean voltage of the region where high DF did not appear was 0.59±1.15 mV (p=0.171). Conclusion High DF site, a parameter representing a localized focal source, had statistically significant but very poor correlations with LA extra-PV voltage substrate in patients with persistent AF.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.