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Background.Reactive oxygen species and particularly free radical induced lipid peroxidative tissue damage have been implicated in the pathogenesis of various renal diseases. Lipid peroxidation is assessed indirectly by the measurement of secondary products, such as malondialdehyde (MDA), using the widely employed thiobarbituric acid reactive substances (TBARS) method. However, this method lacks sensitivity and specificity. We have therefore developed and validated an HPLC (high-performance liquid chromatography) method for measurement of MDA and applied this to a variety of plasma samples in renal patients. [ABSTRACT FROM PUBLISHER]

In the following examples, the time frames and ultimate results are measured in years, not days or months. In particular, the application of genetic techniques to complex systems requires many investigators and a multitude of false leads. The areas chosen are all related to the identification and use of techniques from many scientific fields. Except for the necessity of describing the many years of work required to identify and then utilize the genetic information from yet uncultivated microbes, and identifying the true sources of the dolastatins, the rest of the examples are quite short with commentaries on most of the references given., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

The isolation studies of a crude MeOH/CH 2 Cl 2 (1:1) extract (N005829) of the bark of Laetia corymbulosa yielded 15 new clerodane diterpenes, designated corymbulosins I-W (1-15), as well as four known diterpenes, 16-19. The structures of 1-15 were characterized on the basis of extensive 1D and 2D NMR and HRMS analyses. The absolute configurations of newly isolated compounds 1-15, as well as known 16-19, which were reported previously with only relative configurations, were determined through ECD experiments, X-ray analysis, chemical methods, including Mosher esterification, and comparison of their spectroscopic data. The isolated compounds were evaluated for cytotoxicity against human cancer cell lines. Flow cytometric and immunocytochemical observations of cells treated with cytotoxic clerodanes demonstrated that the chromatin was fragmented and dispersed with formation of apoptotic microtubules.

Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach., (© 2014 Society for Laboratory Automation and Screening.)

Understanding the skin's material properties and natural motion is critical to a myriad of applications from tissue engineering to spacesuits. While there is an extensive understanding of human skin properties based on active tensile testing, both in vitro and in vivo, there is a little current knowledge of the strains experienced by skin during natural movements. Using a motion capture system, we have developed a new technique to measure skin movement and strain around the knee during a squatting motion. With these new data, we are also able to calculate the local direction of lines of nonextension, or contours of the skin that remain a constant length during motion, lines of minimum extension, and lines of minimum compression.

Screening natural product extracts from the National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Using LC-MS analysis to generate chemical structure information on potentially active compounds, two new cyclic hexapeptides, microsclerodermins J ( 1 ) and K ( 2 ), were isolated from the deep-water sponge Microscleroderma herdmani , along with microsclerodermins A ( 3 ) and B ( 4 ), previously isolated from an unidentified Microscleroderma species. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. In vitro antifungal testing showed that the four compounds possessed strong activities against the opportunistic fungal pathogens Candida albicans , C andida glabrata, Candida krusei, Cryptococcus neoformans , and Aspergillus fumigatus .

The National Space Biomedical Research Institute (NSBRI) is supporting the National Aeronautics and Space Administration's (NASA) education mission through a comprehensive Education and Public Outreach Program (EPOP) that communicates the excitement and significance of space biology to schools, families, and lay audiences. The EPOP is comprised of eight academic institutions: Baylor College of Medicine, Massachusetts Institute of Technology, Morehouse School of Medicine, Mount Sinai School of Medicine, Texas A&M University, University of Texas Medical Branch Galveston, Rice University, and the University of Washington. This paper describes the programs and products created by the EPOP to promote space life science education in schools and among the general public. To date, these activities have reached thousands of teachers and students around the US and have been rated very highly., (c2005 Elsevier Ltd. All rights reserved.)

The purpose of this paper is to review the concept of flexibility as discussed in various fields of investigations, to extract its characteristic features, and to explore its implications in the case of aerospace system design. In order to discuss any subject matter clearly, it is necessary to begin with a clear set of definitions. Indeed much can be gained through careful and consistent definitions of terms alone. Flexibility however is a word rich with ambiguity. While it is being increasingly used in various fields, few attempts have been made to formally define, quantify, and propose ways for achieving flexibility. This paper proposes to fill in part of this gap by synthesizing a clear and consistent definition of flexibility. It will do so by reviewing the usage of the term in various fields of inquiries, and show that it is indeed possible to clearly and unambiguously characterize flexibility, and to disentangle it from closely related concepts., (c2003 Elsevier Ltd. All rights reserved.)

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart., (c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.)

The paper reviews the research that has been undertaken to understand and quantify the disturbance effects of the astronaut's motion inside and outside the spacecraft on the vehicle's attitude and acceleratory environment. In early investigations, the dynamic interaction of astronauts, modeled as point masses, and the spacecraft, modelled as a rigid body, was analyzed. Through ground-based experiments and the modeling of astronaut-induced forces and moments as stochastic processes, it became possible to estimate the magnitude and energy content of the loads produced by the astronaut. The first experiment in space to measure the astronaut-induced disturbances was conducted on the Skylab orbital station. Loads generated while performing routine operations were measured on board the Space Shuttle in 1994 and on the space station Mir in 1996-1997., (c 2001 Elsevier Science Ltd. All rights reserved.)

This review of astronaut extravehicular activity (EVA) and the details of American and Soviet/Russian spacesuit design focuses on design recommendations to enhance astronaut safety and effectiveness. Innovative spacesuit design is essential, given the challenges of future exploration-class missions in which astronauts will be called upon to perform increasingly complex and physically demanding tasks in the extreme environments of microgravity and partial gravity.

Characterisation of the kinetics of assembly and dissociation of the HLA class I heterotrimeric complex provides valuable insights into the relative contributions of each element to complex stability. However, to date there has been no real-time binding analysis on whole cells. Here we have developed an optical biosensor model to investigate the binding of class I HLA complexes on whole cells to human beta 2-microglobulin (beta 2m) and the effects of different HLA-specific peptides on this binding. We immobilised beta 2m on an IAsys biosensor surface and established conditions to analyse the binding of this to HLA-A2 expressing cells (T2 cells). Using 721.221 cells as an HLA negative control we showed that HLA-A2 binding was optimal using a) a carboxymethylated dextran surface and b) no growth factors or supplements in the culture medium at the binding event. Using these conditions we verified specificity of binding by inhibition of the reaction with free beta 2m and determined the dissociation rate constant for T2 cell binding to beta 2m (0.03 s-1). In addition, we demonstrated the ability of different HLA specific peptides to modulate cellular HLA-A2 binding to beta 2m. This is the first time that interactions of cell surface HLA class I molecules has been investigated using real-time analysis. Furthermore, our peptide analysis has shown that this model can be used to characterise peptide specific HLA-binding responses on the whole cell surface in real-time.

The main objective of this work was the investigation of passive adsorption and covalent coupling of a polyclonal IgG and a monoclonal preparation of IgG against HSA, to a carboxyl latex particle. The functional activity of the coupled protein was then assessed by quantitative immunoassays for the antigen. Sensitized particles, with different protein coverage, were fully characterized using a range of different technologies, including electrophoretic mobility (µe), photon correlation spectroscopy, and surface plasmon resonance (SPR). The antibody-labeled particles were studied with respect to electrokinetic behavior in pH and ionic strength titration, stability, antibody functionality, and their perfomance in immunoaggregation reactions. Important differences were observed between the two sets of particle preparations throughout the series of experiments. The differences could be attributed to the coupling of the IgG molecules to the particles by the two different adsorption protocols. When proteins were chemically bound to the polymer surface it was necessary to activate the carboxyl groups with a carbodiimide (CDI) moiety that in our case was positively charged. The differences in characteristics between the adsorbed and the coupled antibody particles are thought to be due to the fact that in the covalent coupling protocol some CDI molecules remained linked to the particles, which altered the average electrical state of the outer layer in comparison with those samples where antibodies were physically adsorbed. On the other hand, the isoelectric point of the monoclonal antibody was lower (5.4 +/- 0.1) than the pI of the polyclonal antisera (6.9 +/- 0.9), which could explain why the IgG-latex complexes created with monoclonal molecules were colloidally more stable at neutral pH than those created with the polyclonal antisera. However, no immunoaggregation of antibody particles by the presence of antigen was found with the former. The use of SPR demonstrated that the equilibrium constants for the antibody-antigen recognition of the two antibody preparations were quite similar (KA polyclonal IgG = 2.8 10(8) M-1; KA monoclonal IgG = 9.5 10(7) M-1). These observations suggest that the lack of aggregation mediated by antigen demonstrated by the monoclonal antibody coupled to the latex particles may be due to this protein recognizing only one epitope in the HSA molecule. However, as the repulsive charge between antibody-latex particles counteracts the attractive forces between the antigen epitope and the antibody paratope, the greatest immunoaggregation was obtained when using latex particle-antibody complex with a low charge density (N) in the external layer. Copyright 1998 Academic Press.

Human locomotion in simulated lunar and Martian environments is investigated. A unique human-rated underwater treadmill and an adjustable ballasting harness simulate partial gravity in order to better understand how gravity determines the biomechanics and energetics of human locomotion. This study has two research aspects, biomechanics and energetics. The fundamental biomechanics measurements are continuously recorded vertical forces as exerted by subjects of the treadmill which is instrumented with a force platform. Experimental results indicate that peak vertical force and stride frequency decrease as the gravity level is reduced. Foot contact time is independent of gravity level. Oxygen uptake measurements, VO2, constitute the energetics, or workload, data for this study. As theory predicts, locomotion energy requirements for lunar (1/6-g) and Martian (3/8-g) gravity levels are significantly less than at 1-g. The observed variation in workload with gravity level is nonmonotonic, however, in over half the subject population. The hypothesis is offered that energy expenditure increases for lunar, as compared with Martian, locomotion due to the subject "wasting energy" for stability and posture control in simulated lunar gravity. Biomechanics data could influence advanced spacesuit design and planetary habitat design, while workload data will help define oxygen requirements for planetary life support systems.