Exploring the relationship between zooplankton diel vertical migration and a tertiary nitrite peak in the mesopelagic oxygen minimum zone (OMZ)

Oxygen Minimum Zone (OMZ) is the intense oxygen depletion area located in three main regions, the Eastern South Pacific, Eastern Tropical North Pacific, and the Arabian Sea. The OMZ occurs due to the intense upwelling event supplying the nutrients from bottom to surface. The oxygen concentration is one of the important factors that affect the Dial Vertical Migrating (DVM) zooplanktons behavior. During the day time, DVM zooplankton stays in the core of OMZ to escape their visual oriented predators, and move to the surface during the night time to do the feeding activity. Further, It is believed that this vertically migrating behavior affects the mid water depth nutrients content as DVM zooplankton actively transport the organic matter from surface to mid water depth. But, it is not clear how the DVM zooplankton affects the nutrients content in mid water depth. This study aims to figure out whether the DVM zooplankton affects to the nitrite content in two intense OMZ regions, Eastern South Pacific (ETSP) and the Arabian Sea. Through the ADCP backscatter signal, the abundance of DVM zooplankton and their migrating depth during the day time is calculated. The oxygen and nitrite concentration is collected from several CTD, Niskin bottle, and pump CTD data, and the particle data is collected from UVP5. By using these data, we estimated the relationship between them. In addition to the secondary nitrite maximum, we found another nitrite maximum, which has can be distinguishable from secondary nitrite maximum. We named this nitrite maximum as ’tertiary nitrite maximum’. In both ETSP and the Arabian Sea, the tertiary nitrite maximum occurred in very intense oxygen regions. Especially, the tertiary nitrite maximum occurs if; 1) the oxygen concentration is less than 1 �mol kg-1, 2) DVM zooplankton goes deeper than the depth at which secondary nitrite maximum occurred. The regression analysis between the abundance of DVM zooplankton (calculated from ADCP backscatter signal) and tertiary nitrite concentration in midwater depth shows a significant positive relationship (Pearson r= 0.50, p<0.02). Further, the comparison between the secondary nitrite maximum and tertiary nitrite maximum shows a significant positive relationship (Pearson r=0.68, p<0.05), and the relative average ratio is 0.94. These result may imply DVM zooplankton actively export the organic nitrogen from surface to mid-water depth and thereby fuel the denitrification process, which will eventually drive the N loss in the ocean. thereby fuel the denitrification process, which will eventually drive the N loss in the ocean

Evaluation of Frequency Dependent Equivalent Linear analysis

One dimensional equivalent linear site response analysis is widely used in practice due to the simplicity and ease of use. In the method, the dynamic soil properties are assumed to be independent of the loading frequency. To better simulate the nonlinear behavior, equivalent analysis methods that models the loading frequency dependence of the shear modulus and damping were developed. The backbone of the methods is the frequency-dependent shear strain curves. Various forms of the frequency-dependent shear strain curves were developed. However, the effect of the frequency - shear strain curves are not well known and documented. In this study, a series of frequency – strain curves were used to evaluate the accuracy of the frequency dependent equivalent linear analysis. Results show that the effect of the curves is significant and that the frequency dependent analysis does not always provide an improved estimate and can highly overestimate the amplification of the high frequency components of the ground motion. The degree of overestimation is dependent on the characteristics of the input ground motion and the soil profile. It is therefore concluded that the frequency dependent equivalent linear analysis should be used with caution and that standard equivalent linear analysis can be a more reliable option

Base extrusion is found at helical junctions between right- and left-handed forms of DNA and RNA

Base extrusion is a major structural feature at the junction between B- and Z-DNA (the B–Z junction) where a base pair is broken, and the two bases are extruded from the double helix. Despite the demonstration of base extrusion at the B–Z junction, it is not clear whether a similar base extrusion occurs at other types of junctions involving the left-handed Z conformation. Here, we investigate structural changes of bases at three Z-form junctions: DNA B–Z and Z–Z and RNA A–Z junctions. By monitoring fluorescently labeled duplex nucleic acids using 2-aminopurines at various positions relative to the junction point, we show that base extrusion occurs not only at the DNA B–Z junction, but also at the RNA A–Z and DNA Z–Z junctions. Our data suggest that base extrusion is a general feature of Z-form nucleic-acid junctions.Korean Science and Engineering Foundation (grant NRL-2006-02287)Korea (South). Ministry of Science and Technology (21C Frontier Functional Proteomics Program FPR08B2-270)Korean Science and Engineering Foundation (Ubiquitome Research Program M105 33010001-05N3301-00100)Korea Research Foundation (MOEHRD, Basic Research Promotion Fund; KRF-2005-070-C00078

Characterization of DNA-binding activity of Zα domains from poxviruses and the importance of the β-wing regions in converting B-DNA to Z-DNA

The E3L gene is essential for pathogenesis in vaccinia virus. The E3L gene product consists of an N-terminal Zα domain and a C-terminal double-stranded RNA (dsRNA) binding domain; the left-handed Z-DNA-binding activity of the Zα domain of E3L is required for viral pathogenicity in mice. E3L is highly conserved among poxviruses, including the smallpox virus, and it is likely that the orthologous Zα domains play similar roles. To better understand the biological function of E3L proteins, we have investigated the Z-DNA-binding behavior of five representative Zα domains from poxviruses. Using surface plasmon resonance (SPR), we have demonstrated that these viral Zα domains bind Z-DNA tightly. Ability of Zα[subscript E3L] converting B-DNA to Z-DNA was measured by circular dichroism (CD). The extents to which these Zαs can stabilize Z-DNA vary considerably. Mutational studies demonstrate that residues in the loop of the β-wing play an important role in this stabilization. Notably the Zα domain of vaccinia E3L acquires ability to convert B-DNA to Z-DNA by mutating amino acid residues in this region. Differences in the host cells of the various poxviruses may require different abilities to stabilize Z-DNA; this may be reflected in the observed differences in behavior in these Zα proteins.Korean Science and Engineering Foundation (National Research Laboratory Program (NRL-2006-02287))Korean Science and Engineering Foundation (Ubiquitome Research Program (M10533010002-06N3301-00210))Korean Science and Engineering Foundation (21C Frontier Functional Proteomics Program (FPR06B2-120))National Institutes of Health (U.S.)Ellison Medical FoundationKorea (South). Ministry of Science and Technology (National Laboratory program (NRL-2006-02287)

CRISPR RNAs trigger innate immune responses in human cells

Here, we report that CRISPR guide RNAs (gRNAs) with a 5'-triphosphate group (5'-ppp gRNAs) produced via in vitro transcription trigger RNA-sensing innate immune responses in human and murine cells, leading to cytotoxicity. 5'-ppp gRNAs in the cytosol are recognized by DDX58, which in turn activates type I interferon responses, causing up to similar to 80% cell death. We show that the triphosphate group can be removed by a phosphatase in vitro and that the resulting St-hydroxyl gRNAs in complex with Cas9 or Cpfl avoid innate immune responses and can achieve targeted mutagenesis at a frequency of 95% in primary human CD4(+) T cells. These results are in line with previous findings that chemically synthesized sgRNAs with a 5'-hydroxyl group are much more efficient than in vitro-transcribed (IVT) sgRNAs in human and other mammalian cells. The phosphatase treatment of IVT sgRNAs is a cost-effective method for making highly active sgRNAs, avoiding innate immune responses in human cells.

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer

Purpose: To identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). Materials and methods: Among 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. Results: Median follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). Conclusion: Three prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended. (C) 2020 Elsevier B.V. All rights reserved.

Effect of beraprost sodium on arterial stiffness in patients with type 2 diabetic nephropathy

Trial registration : ClinicalTrials.gov number NCT01796418Background : Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). Cardiovascular (CV) complications are the most common cause of death among ESRD patients. Beraprost sodium (BPS) is a prostacyclin analog with vasodilatory and antiplatelet effects. Methods : This is a multicenter prospective, randomized, double-blind, placebo-controlled trial to determine whether treatment with BPS improves arterial stiffness in patients with type 2 diabetic nephropathy. A total of 102 participants with type 2 diabetic nephropathy will be screened, enrolled, and randomly assigned to receive either 80 μg BPS or placebo daily for 12 weeks. The primary outcome is the change in brachial-ankle pulse wave velocity between baseline and after 12 weeks of medication use. The secondary outcomes will include changes in the ankle-brachial index, the urine albumin to creatinine ratio, the estimated glomerular filtration rate, lipid profiles, and blood pressure from baseline to after treatment. Discussion : This clinical trial is the first to investigate the effects of BPS on changes in CV biomarkers, albuminuria, renal function, and lipid profiles in patients with diabetic nephropathy.Peer Reviewe

Evaluation of the physicochemical, metabolomic, and sensory characteristics of Chikso and Hanwoo beef during wet aging

Objective This study aimed to evaluate the physicochemical, metabolomic, and sensory qualities of Chikso and Hanwoo beef during 28 days of wet aging. Methods Rump and loins from Hanwoo and Chikso were obtained and wet-aged for 28 days at 4°C. The samples were collected at 7-day interval (n = 3 for each period). Physicochemical qualities including pH, meat color, shear force value, and myofibrillar fragmentation index, metabolomic profiles, and sensory attributes (volatile organic compounds and relative taste intensities) were measured. Results Chikso showed a significantly higher shear force value than Hanwoo on day 0; however, no differences between breeds were found after day 14, regardless of the cuts. Overall, Chikso had more abundant metabolites than Hanwoo, especially L-carnitine and tyrosine. Among the volatiles, the ketone ratio was higher in the Chikso rump than the Hanwoo rump; however, Chikso had fewer alcohols and aldehydes than Hanwoo. Chikso rump showed higher taste intensities than the Hanwoo rump on day 0, and sourness decreased in Chikso, but increased in the Hanwoo rump on day 14. Wet aging for 14 days intensified the taste of Chikso loin but reduced the umami intensity of Hanwoo loin. Conclusion Chikso had different metabolomic and sensory characteristics compared to Hanwoo cattle, and 14 days of wet aging could improve its tenderness and flavor traits

Treatment outcomes of re-irradiation using stereotactic ablative radiotherapy to lung: a propensity score matching analysis

Background The purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor. Methods A retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54Gy (range 48–60Gy), and the median fraction number was 4 (range 4–6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort. Results The 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%, P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity. Conclusions The local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable