Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV β-lactamase on hydrolysis of penicillin and ampicillin

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyze the significance of leucine to proline substitution at position 138(Leu138Pro) on the hydrolysis of penicillin and ampicillin that we identified in the <it>bla</it>_SHVgene of clinical <it>Escherichia coli </it>swine isolate.</p> <p>Results</p> <p>Kinetic analysis of the mutant proteins showed that <it>K</it>_{<it>m </it>}value of the purified L138P mutant was comparatively higher than SHV-1, SHV-33 and SHV-33(L138P) enzyme for penicillin and ampicillin. Docking simulation of the SHV-1 and SHV-(L138P) enzymes also confirmed that β-lactamases preferred penicillin to ampicillin and the SHV-1 had a higher binding affinity for antibiotics compared to the SHV-(L138P) and other mutants.</p> <p>Conclusions</p> <p>Our result demonstrated that L138P has a reduced role in penicillin and ampicillin hydrolyzing properties of SHV β-lactamases. These naturally occurring mutations rendering reduced function of the existing protein could trigger the emergence or acquisition of more effective alternative mechanisms for β-lactam hydrolysis.</p

Development of Practical Design Approaches for Water Distribution Systems

The optimal design of water distribution systems (WDSs) should be economical, consider practical field applicability, and satisfy hydraulic constraints such as nodal pressure and flow velocity. However, the general optimal design of a WDSs approach using a metaheuristic algorithm was difficult to apply for achieving pipe size continuity at the confluence point. Although some studies developed the design approaches considering the pipe continuity, these approaches took many simulation times. For these reasons, this study improves the existing pipe continuity search method by reducing the computation time and enhancing the ability to handle pipe size continuity at complex joints that have more than three nodes. In addition to more practical WDSs designs, the approach considers various system design factors simultaneously in a multi-objective framework. To verify the proposed approach, the three well-known WDSs to apply WDS design problems are applied, and the results are compared with the previous design method, which used a pipe continuity research algorithm. This study can reduce the computation time by 87% and shows an ability to handle complex joints. Finally, the application of this practical design technique, which considers pipe continuity and multiple design factors, can reduce the gap between the theoretical design and the real world because it considers construction conditions and abnormal situations.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Human microglial cells synthesize albumin in brain

Albumin has been implicated in Alzheimer&#x27;s disease since it can bind to and transport amyloid beta, the causative agent; albumin is also a potent inhibitor of amyloid beta polymerization. In a pilot phase study of Human Brain Proteome Project, we found evidence that albumin may be synthesized in immortalized human microglial cells, human primary microglial cells, and human fetal and adult brain tissues. We also found the synthesis and secretion is enhanced upon microglial activation by Amyloid [beta]~1-42~, lipopolysaccharide treatment or human Alzheimer&#x27;s brain

Orbital Variations of Biogenic CaCO3 and Opal Abundance in the Western and Central Equatorial Pacific Ocean During the Late Quaternary

Biogenic CaCO3 and opal abundances were measured in two piston cores (PC313 and PC5101) collected, respectively, along the equator in the western and central Pacific Ocean. The age model for core PC313, which extends to about 750 ka, was developed by comparing the oxygen isotope stratigraphy of planktonic foraminifera (N. dutetrei) to the SPECMAP stack. The age model for core PC5101, which extends to about 600 ka, was developed by stratigraphic correlation of CaCO3 contents to those in the well-dated core RC11-210 (Chuey et al. 1987). Both cores distinctly exhibited a series of CaCO3 and opal variations, which are mainly controlled by the orbital eccentricity cycle of about 100-kyr. The orbital-scale cyclic variations of CaCO3 and opal contents appear to be contrasting in both cores such that high CaCO3 and low opal contents occurred during the glacial periods. In contrast, during the interglacial periods, low CaCO3 and high opal contents occurred. Mostly remarkable is the distinct occurrence of a mid-Bruhnes event (MBE) at around 350 ka. The CaCO3 content was higher in core PC5101 than in core PC313 before the MBE, whereas biogenic opal abundance became higher in core PC5101 after the MBE. Such a characteristic discrepancy of biogenic (CaCO3 and opal) production, i.e., a succession of primary producers from coccolithophore to diatom, between cores PC313 and PC5101 may be attributed to the prevailing dominant hydrographic conditions (i.e., the South Equatorial Current), in the path of which both cores are located. The intensity of westward propagation might have been an important factor in contrasting biogenic production centering around the MBE

Clinical Characteristics and Risk Factors for Nosocomial Candidemia in Medical Intensive Care Units: Experience in a Single Hospital in Korea for 6.6 Years

The aim of this study was to determine candidemia incidence among patients in a medical intensive-care unit (MICU) and the associated mortality rate and to identify risk factors associated with candidemia. We retrospectively performed a 1:3 matched case-control study of MICU patients with candidemia. Controls were matched for sex, age, and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Candidemia incidence was 9.1 per 1,000 admissions. The most common pathogen was Candida albicans. Crude mortality was 96% among candidemia patients and 52% among controls (P<0.001). Mortality differed significantly between the groups according to Kaplan-Meier survival analysis (P=0.024). Multivariate analysis identified the following independent risk factors for candidemia: central venous catheterization (odds ratio [OR] = 3.2, 95% confidence interval [CI]=1.2-9.0), previous steroid therapy (OR=4.7, 95% CI=1.8-12.1), blood transfusion during the same admission period (OR=6.3, 95% CI=2.4-16.7), and hepatic failure upon MICU admission (OR=6.9, 95% CI=1.7-28.4). In conclusion, we identify an additional independent risk factor for candidemia, the presence of hepatic failure on MICU admission. Therefore, increased awareness of risk factors, including hepatic failure, is necessary for the management of candidemia

Hydrogen effects on nanomechanical behavior of additively manufactured 316L stainless steels

Additive manufacturing (AM) has received considerable attention in recent years due to its ability to produce complex engineering components with reduced cost and waste, which simply cannot be made with conventional manufacturing processes. It has been reported that AM 316L austenitic stainless steel (SS) has excellent mechanical properties and possibly even breaks the strength-ductility trade-off. For practical industrial application, it is necessary to investigate the AM steel\u27s resistance to hydrogen embrittlement which is unavoidable in most strucral applications. In this work, we explore the hydrogen effects on nanomechanical responses of AM 316L SS (such as hardness, strain rate sensitivity, activation volume). The obtained results will be compared with those of conventional 316L SS and discussed in terms of hydrogen effect on plastic deformation and microstructure. Please click Additional Files below to see the full abstract

Effects of Rhythmic Auditory Stimulation During Hemiplegic Arm Reaching in Individuals with Stroke: An Exploratory Study

SummaryObjective/BackgroundThis study investigated the effects of rhythmic auditory stimulation (RAS) on muscle activity and elbow motion during arm reaching with hemiplegic arm in participants with stroke.MethodsSixteen adults with stroke who resided in a community were recruited in this study. The RAS consisted of sound emitted from a digital metronome. While sitting upright in a chair, participants reached their arms towards a target (a switch on a table) both with and without RAS. The three-dimensional motion analysis system and surface electromyography system were used for measurements during the reaching tasks.ResultsWe found that RAS elicited better performance in reaching movements than those movements performed without RAS. RAS shortened the movement time (p = .002), reduced the change in acceleration (p = .001), increased the elbow extension range of motion (p = .001), increased muscle activation of the triceps brachii (p = .024), and reduced the co-contraction ratio (p = .015) of the affected arm.ConclusionRAS might be a useful technique to facilitate improvements in motor function of the affected arm in patients with stroke