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)

When and why to start continuous renal replacement therapy in critically ill patients with acute kidney injury

Acute kidney injury (AKI) is a common condition in critically ill patients, and may contribute to significant medical, social, and economic consequences, including death. Although there have been advances in medical technology, including continuous renal replacement therapy (CRRT), the mortality rate of AKI is high, and there is no fundamental treatment that can reverse disease progression. The decision to implement CRRT is often subjective and based primarily on the clinician’s judgment without consistent and concrete guidelines or protocols regarding when to initiate and discontinue CRRT and how to manage complications. Recently, several randomized controlled trials addressing the initiation of renal replacement therapy in critically ill patients with AKI have been completed, but clinical application of the findings is limited by the heterogeneity of the objectives and research designs. In this review, the advantages and disadvantages of CRRT initiation, clinical guideline recommendations, and the results of currently published clinical trials and meta-analyses are summarized to guide patient care and identify future research priorities

Identification of C16orf74 as a Marker of Progression in Primary Non-Muscle Invasive Bladder Cancer

PURPOSE: Methylation-induced silencing of PRSS3 has been shown to be significantly associated with invasive bladder cancer, and expression of the C16orf74 gene locus has been shown to correlate positively with PRSS3. The aim of the current study was to evaluate the relationship between C16orf74 expression level and progression in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: C16orf74 mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis of 193 tumor specimens from patients with primary NMIBC. Expression data were analyzed in terms of clinical and experimental parameters. Kaplan-Meier curves and multivariate Cox regression models, respectively, were used to determine progression-free survival and to identify independent predictive parameters of progression. RESULTS: Analysis using Kaplan-Meier curves revealed prolonged progression-free survival of high-C16orf74-expressors as compared to low-expressors (p<0.001). Multivariate Cox regression analysis revealed that low C16orf74 mRNA expression levels are a significant risk factor for disease progression in patients with primary NMIBC (HR: 10.042, CI:2.699-37.360, p = 0.001). CONCLUSIONS: Decreased expression of C16orf74 correlates significantly with progression in primary NMIBC. C16orf74 expression level represents a potentially useful marker for predicting progression in primary NMIBC patients

The behavior characteristics of a reservoir levee subjected to increasing water levels

Centrifugal model testing has been widely used to study the stability of levees. However, there have been a limited number of physical studies on levees where the velocity of increasing water levels was considered. To investigate the behavior characteristics of reservoir levees with different velocities of increasing water levels, centrifugal model tests and seepage-deformation coupled analyses were conducted. Through this study, it was confirmed that increasing water levels at higher velocities induces dramatic increases in the displacement, plastic volumetric strain and risk of hydraulic fracturing occurring in the core of the levee. Hence, real-time monitoring of the displacement and the pore water pres­sure of a levee is important to ensure levee stability

Role of increased neutrophil extracellular trap formation on acute kidney injury in COVID-19 patients

BackgroundA strong association between elevated neutrophil extracellular trap (NET) levels and poor clinical outcomes in patients with coronavirus infection 2019 (COVID-19) has been reported. However, while acute kidney injury (AKI) is a common complication of COVID-19, the role of NETs in COVID-19-associated AKI is unclear. We investigated the association between elevated NETs and AKI and the prognostic role of NETs in COVID-19 patients.MethodsTwo representative markers of NETs, circulating nucleosomes and myeloperoxidase-DNA, were measured in 115 hospitalized patients. Serum levels of interleukin [IL]-6, monocyte chemotactic protein-1 [MCP-1], plasma von Willebrand factor (vWF) and urinary biomarkers of renal tubular damage (β2-microglobulin [β2M] and kidney injury molecule 1 [KIM-1]) were measured.ResultsAKI was found in 43 patients (37.4%), and pre-existing chronic kidney disease (CKD) was a strong risk factor for AKI. Higher circulating NET levels were a significant predictor of increased risk of initial ICU admission, in-hospital mortality (adjusted HR 3.21, 95% CI 1.08–9.19) and AKI (OR 3.67, 95% CI 1.30-10.41), independent of age, diabetes, pre-existing CKD and IL-6 levels. There were strong correlations between circulating nucleosome levels and urinary KIM-1/creatinine (r=0.368, p=0.001) and β2M (r=0.218, p=0.049) levels. NETs were also strongly closely associated with serum vWF (r = 0.356, p&lt;0.001), but not with IL-6 or MCP-1 levels.ConclusionsElevated NETs were closely associated with AKI, which was a strong predictor of mortality. The close association between NETs and vWF may suggest a role for NETs in COVID-19-associated vasculopathy leading to AKI

Singlet fermionic dark matter

We propose a renormalizable model of a fermionic dark matter by introducing a gauge singlet Dirac fermion and a real singlet scalar. The bridges between the singlet sector and the standard model sector are only the singlet scalar interaction terms with the standard model Higgs field. The singlet fermion couples to the standard model particles through the mixing between the standard model Higgs and singlet scalar and is naturally a weakly interacting massive particle (WIMP). The measured relic abundance can be explained by the singlet fermionic dark matter as the WIMP within this model. Collider implication of the singlet fermionic dark matter is also discussed. Predicted is the elastic scattering cross section of the singlet fermion into target nuclei for a direct detection of the dark matter. Search of the direct detection of the dark matter provides severe constraints on the parameters of our model.Comment: 12 pages, 7 figure

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

Acute Myocardial Infarction by Right Coronary Artery Occlusion Presenting as Precordial ST Elevation on Electrocardiography

It is rare to observe ST-segment elevation in only the anterior leads and not the inferior leads during right coronary artery occlusion. We describe a case with acute myocardial infarction (MI) by right coronary artery occlusion who developed ST-segment elevation only in the precordial leads V1 to V3