Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA)

The (Mtb) pathogen encodes an -acetylglucosamine-6-phosphate deacetylase enzyme, NagA (Rv3332), that belongs to the amidohydrolase superfamily. NagA enzymes catalyze the deacetylation of -acetylglucosamine-6-phosphate (GlcNAc6P) to glucosamine-6-phosphate (GlcN6P). NagA is a potential anti-tubercular drug target because it represents the key enzymatic step in the generation of essential amino-sugar precursors required for cell wall biosynthesis and also influences recycling of cell wall peptidoglycan fragments. Here, we report the structural and functional characterization of NagA from (MSNagA) and (MMNagA), close relatives of Using a combination of X-ray crystallography, site-directed mutagenesis, and biochemical and biophysical assays, we show that these mycobacterial NagA enzymes are selective for GlcNAc6P. Site-directed mutagenesis studies revealed crucial roles of conserved residues in the active site that underpin stereo-selective recognition, binding, and catalysis of substrates. Moreover, we report the crystal structure of MSNagA in both ligand-free form and in complex with the GlcNAc6P substrate at 2.6 Å and 2.0 Å resolutions, respectively. The GlcNAc6P-complex structure disclosed the precise mode of GlcNAc6P binding and the structural framework of the active site, including two divalent metals located in the α/β binuclear site. Furthermore, we observed a cysteine residue located on a flexible loop region that occludes the active site. This cysteine is unique to mycobacteria and may represent a unique subsite for targeting mycobacterial NagA enzymes. Our results provide critical insights into the structural and mechanistic properties of mycobacterial NagA enzymes having an essential role in amino-sugar and nucleotide metabolism in mycobacteria

Clinicopathologic Characteristics of Multifocal Gastric Adenocarcinoma

BACKGROUNDANDOBJECTIVE: Gastric cancer is the fifth prevalent cancer in worldwide. Among of this, adenocarcinoma is more than 95% of all case and most prevalent. According to gastric adenocarcinoma is resistant to adjuvant therapy, surgical resection is the cardinal strategies of treatment. One of the problems with treating adenocarcinoma of the stomach is that its main causes are malignant or pre-malignant changes in the residual gastric tissue that may be neglected during resection. By recognizing these lesions and resection, they can be expected to reduce the malignancy. Therefore, this study was conducted to investigate the characteristics of non-tumoral gastric tissue in terms of malignant or pre-malignant changes. METHODS: In this retrospective cross-sectional study, 112 patients who had undergone total gastrectomy in the hospitals affiliated to Babol University of Medical Sciences during the period of 2013-2017 were examined and analyzed for age, sex, type and location of tumor. FINDINGS: Of 112 cases that studied,72 cases (64.3%) were male and 40 cases (35.7%) were female. The mean of ages was 64.7±8.6 year. Poorly differentiated pathology in 60.7% and well differentiated pathology in 39.3% of patients were seen. In 64 patients (57%), there was synchronous lesions in addition to primary pathology. These synchronous lesions were related statistically significant to pathology, cancer stage and gender. CONCLUSION: Based on the results of this study, it can be concluded that resection should be accompanied by considering simultaneous lesions in addition to primary pathology, which can be a reason for total gastrectomy as a standard treatment for gastric cancer

The economic value of rapid deployment aortic valve replacement via full sternotomy

Aim: To compare the economic value of EDWARDS INTUITY EliteTM (EIE) valve system for rapid-deployment aortic valve replacement (RDAVR) in a full sternotomy (FS) approach (EIE-FS-RDAVR) versus FS-AVR using conventional stented bioprosthesis. Data & methods: A simulation model to compare each treatment’s 30-day inpatient utilization and complication rates utilized: clinical end points obtained from the TRANSFORM trial patient subset (EIE-FS-RDAVR) and a best evidence review of the published literature (FS-AVR); and costs from the Premier database and published literature. Results: EIE-FS-RDAVR costs $800 less than FS-AVR per surgery episode attributable to lowered complication rates and utilization. Combined with the lower mortality, EIE-FS-RDAVR was a superior (dominant) technology versus FS-AVR. Conclusion: This preliminary investigation of EIE-FS-RDAVR versus conventional FS- AVR found the EIE valve offered superior economic value over a 30-day period. Real- world analyses with additional long-term follow-up are needed to evaluate if this result can be replicated over a longer timeframe

The effect of adsorbed volatile organic compounds on an ultrathin water film measurement

Using surface plasmon resonance imaging (SPRi), we have recently shown for the first time the existence of a monolayer water film between droplets during dropwise condensation. This study examines the effect of adsorbed volatile organic compounds (VOCs) on the ultrathin film measurement using SPRi. Further, the work presents the proper surface-treatment process that enables measurements of the ultrathin water layer during high-speed imaging of dropwise condensation at 3000 frame per second. In this study, two methods were applied for cleaning the surface (gold-coated glass)-(1) standard cleaning procedure (SCP) using acetone, isopropyl alcohol, and deionized water and (2) SCP followed by air plasma cleaning. This work discusses the effect of the cleaning procedures on surface roughness, contact angle, and surface chemistry using atomic force microscopy, optical microscopy, and an X-ray photoelectron spectroscope meter. The results showed that SCP before the SPRi is a proper surface-treatment method. The effect of adsorbed VOCs during dropwise condensation on a surface treated with SCP was measured to be 0.0025 (reflectivity unit), which was 70% smaller than the reflectance associated with a monolayer water film. The results of this work confirm a monolayer water film observation during the dropwise condensation, which has been reported before

Experimental Study of Subcooled Boiling Heat Transfer of Axial and Swirling Flows inside Mini Annular Gaps

An experimental study of the subcooled boiling heat transfer of axial and swirling upward flows inside vertical mini annular gaps was conducted using deionized water. The subcooled boiling heat transfer coefficients and the boiling curves of the flow inside mini annular gaps with different gap sizes have been investigated. The experimental results both for the single phase heat transfer and subcooled boiling heat transfer inside mini annular gaps showed very good agreement with correlations in the literature. The results showed that the subcooled boiling heat transfer coefficient for a given heat flux increases as the size of the annular gap is decreased. The maximum wall superheat is also influenced negligibly by mass flux. Furthermore, the effects of swirl flow by using spring insets inside the mini annuli on the single phase and subcooled boiling heat transfer have been studied. The results showed that the single phase and subcooled boiling heat transfer coefficients are increased by having swirl flow inside mini annuli using spring inserts. The obtained results also showed that the heat transfer enhancement by having swirl flow inside the annuli using spring inserts decreases as the applied heat flux is increased in the subcooled boiling heat transfer region

Pathogenic variability in Exserohilum turcicum and identification of resistant sources to turcicum leaf blight of maize (Zea mays L.)

Turcicum leaf blight of maize incited by Exserohilum turcicum (Pass.) Leonard and Suggs is the major limiting factor of maize production in temperate agro-ecologies. Disease management through host plant resistance is the most effective strategy. In the present study among 26 maize genotypes which were initially screened for resistance against E. turcicum under field conditions, 8 genotypes viz., PS 39, CML 451, CML 470, CML 472, VL 1030, VL 1018140, VL1018527 and SMI178-1 were found resistant when screened against twelve isolates of E. turcicum under artificial epiphytotic conditions. Eight genotypes viz., PS45, CML165, CML459, VL1249, VL0536, SMC-5, SMC-3 and KDL 211 were found moderately resistant with disease grade ranged from 2.1-2.5. These maize genotypes possess resistance to turcicum leaf blight can be used successfully in developing high yielding early maturing varieties for high altitude temperate agro-ecologies. The fungus E. turcicum is highly variable in nature. Variability studies on pathogenicity were conducted on twelve isolates of E. turcicum on eleven putative differential maize lines. During the present study a wide pathogenic variation was observed among the twelve isolates of E. turcicum. Cluster analysis on the basis of similarity or dissimilarity in reaction types exhibited by the differential hosts, clustered the isolates into 6 pathogenic groups. The isolates belonged to higher altitudes (Kti 10, Kti11, Kti5) were found to be more aggressive as compared to the isolates of low altitude areas

Risk factors associated with heart valve thrombosis in patients with prosthetic heart valve dysfunction

Background: Thrombotic and thromboembolic events are important causes of mortality and morbidity in patients with prosthetic heart valve. The aim of this study is to evaluate the factors that may contribute to prosthetic heart valve thrombosis. Methods: This was a cross-sectional study in Rajaie Heart Center on patients with prosthetic heart valve malfunction, within a year. According to the echocardiographic and fluoroscopic findings, the patients were divided into two groups (thrombosis and non-thrombosis groups). The patients' demographic, clinical and laboratory data were recorded and analyzed with SPSS software. Results: A total of 142 patients participated in this study. Ninety-four patients (66.2) were diagnosed with thrombosis. There was a significant relationship between thrombosis and inadequate anti-coagulation (international normalized rati INR <2.5) (odds ratio OR: 4.15, 95% CI: 1.98-9.87, P = 0.003), history of infection (OR: 12.81, 95% CI: 3.52-19.02, P < 0.001), prothrombin time (PT) check interval (OR: 2.38, 95% CI: 1.63-8.47, P = 0.019), atrial fibrillation (AF) rhythm (OR: 3.96, 95% CI: 1.75-8.09, P = 0.019), and plasma fibrinogen level (OR: 6.90, 95% CI: 2.58-14.69). Conclusion: Based on this study, inadequate anti-coagulation, AF rhythm, recent infection and plasma fibrinogen level were the factors most contributing to prosthetic valve thrombosis. As there were many cases of thrombosis in patients with history of infection, this factor can be considered for risk assessment in prosthetic valve. © 2020 The Author(s)