Applications in Bioastronautics and Bioinformatics: Early Radiation Cataracts Detected by Noninvasive, Quantitative, and Remote Means

Human exploration of Mars is a key goal in NASA's exploration planning in the next 20 years. Maintaining crew health and good vision is certainly an important aspect of achieving a successful mission. Continuous radiation exposure is a risk factor for radiation-induced cataracts in astronauts because radiation exposure in space travel has the potential of accelerating the aging process (ref. 1). A patented compact device (ref. 2) based on the technique of dynamic light scattering (DLS) was designed for monitoring an astronaut's ocular health during long-duration space travel. This capability of early diagnosis, unmatched by any other clinical technique in use today, may enable prompt initiation of preventive/curative therapy. An Internet web-based system integrating photon correlation data and controlling the hardware to monitor cataract development in vivo at a remote site in real time (teleophthalmology) is currently being developed. The new technology detects cataracts very early (at the molecular level). Cataract studies onboard the International Space Station will be helpful in quantifying any adverse effect of radiation to ocular health. The normal lens in a human eye, situated behind the cornea, is a transparent tissue. It contains 35 wt % protein and 65 wt % water. Aging, disease (e.g., diabetes), smoking, dehydration, malnutrition, and exposure to ultraviolet light and ionizing radiation can cause agglomeration of the lens proteins. Protein aggregation can take place anywhere in the lens, causing lens opacity. The aggregation and opacification could produce nuclear (central portion of the lens) or cortical (peripheral) cataracts. Nuclear and posterior subcapsular (the membrane's capsule surrounds the whole lens) cataracts, being on the visual optical axis of the eye, cause visual impairment that can finally lead to blindness. The lens proteins, in their native state, are small in size. As a cataract develops, this size grows from a few nanometers (transparent) to several micrometers (cloudy). Ansari and Datiles have shown that DLS can detect cataracts at least two to three orders of magnitude earlier noninvasively and quantitatively than the best imaging (Scheimpflug) techniques in clinical use today (ref. 3)

GLUTAREDOXIN 2 (GRX2) KNOCKOUT INCREASES SENSITIVITY TO OXIDATIVE STRESS IN MOUSE LENS EPITHELIAL CELLS

Glutaredoxin belongs to the oxidoreductase family with cytosolic glutaredoxin 1 (Grx1) and mitochondrial gluraredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper studied the effect of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild type (WT) mice. We found that both cell types showed similar growth patterns and morphology, and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin (Trx) expression but exhibited high sensitivity to oxidative stress. Under treatment of H2O2, the KO cells showed less viability, higher membrane leakage, enhanced ATP loss and complex I inactivation, and weakened ability to detoxify H2O2 in comparison with that of the WT cells. The KO cells had higher glutathionylation in the mitochondrial proteins, particularly the 75-kDa subunit of complex I. Recombinant Grx2 deglutathionylated complex I, and restored most of its activity. We conclude that Grx2 has a function to protect cells against H2O2-induced injury via its peroxidase and dethiolase activities; particularly, Grx2 prevents complex I inactivation and preserves mitochondrial function

Glutathione in calf trabecularmeshwork and its relation to aqueous humor outflow facility,”

Previous studies have shown that sulfhydryl reagents can alter the facility of aqueous humor outflow but little is known about the sulfhydryl constituents of the aqueous outflow system or the effect of oxidants upon outflow facility. In the present study the concentration of glutathione (GSH) was measured in excised calf trabecular meshwork (TM) and found to be 0.40 n mol/g wet wt (0.027 n mol/mg protein). Oxidized glutathione was not detectable in the tissue. TM was found to have significant hexose monophosphate shunt activity as determined by measurement of the oxidation of 14C-1 and 14C-6-labeled glucose in tissue homogenates. The concentration of GSH in TM of enucleated calf eyes could be totally depleted by infusion of medium containing both diamide, which is an oxidant of GSH, and l,3bis(2-chlorethyl)-l-nitrosourea (BCNU), which is an inhibitor of the enzyme glutathione reductase. The depletion of GSH was found to have no effect on the facility of aqueous outflow. Experiments were also done in which normal and TM GSH-depleted eyes were perfused with medium containing H202. Exposure to H202 produced no effect on outflow facility in the normal eyes but caused a 33% decrease in facility in eyes with the GSH-depleted TM. The results indicate that GSH may not participate directly in regulating aqueous humor outflow but is able to protect TM against H202-induced oxidative damage that would otherwise lead to a decrease in outflow facility. Invest Ophthalmol Vis Sci 24:1283-1287, 1983 Anterior chamber perfusion studies have shown that the presence of sulfhydryl (-SH) reagents can alter the resistance to aqueous humor outflow, 1 " 3 which suggests that thiols present in the trabecular meshwork (TM) may be involved in modulating aqueous humor outflow resistance. One thiol that may be involved in this process is glutathione (GSH), which has been found to be present in a number of ocular tissues 4 " 6 but whose concentration has not been determined in TM. The present study was designed to determine the level of GSH present in calf TM and to investigate its function. In addition, since the hexose monophosphate shunt (HMPS) is an integral part of GSH metabolism, 7 the presence of this pathway in TM was also investigated. Since our studies to be reported demonstrated the presence of GSH in TM, it was of interest to deplete the level of the tripeptide in TM of perfused calf eyes and study the effect on aqueous outflow facility. For this purpose advantage was taken of diamide that has been shown to be a relatively specific oxidant of GSH 8 and of l,3bis(2-chloroethyl)-l-nitrosourea (BCNU), which is a specific inhibitor of the enzyme glutathione reductase. 9 Of special importance was the possible interaction of GSH in TM with H202, an oxidant that has been found to be a normal constituent of aqueous humor in at least three species including man. " 12 Since aqueous humor is drained via the TM it is conceivable that oxidant stresses that exceed the capacity of TM for detoxification could result in cellular damage and subsequent alteration of aqueous humor outflow resistance. We report here on changes that occur in the facility of aqueous outflow in calf eyes when GSH-depleted TM is exposed to H202. Materials and Methods Calf eyes were obtained from Joseph T. Trelegan and Co. (Cambridge, MA). Shortly after the animals were killed by exsanguination the eyes were enucleated and placed in iced saline solution for transportation and use within 24 hrs. Lenses used in the study were from albino rabbits weighing between 1.8 and 2.2 kg

Partitioning of on-demand electron pairs

We demonstrate the high fidelity splitting of electron pairs emitted on demand from a dynamic quantum dot by an electronic beam splitter. The fidelity of pair splitting is inferred from the coincidence of arrival in two detector paths probed by a measurement of the partitioning noise. The emission characteristic of the on-demand electron source is tunable from electrons being partitioned equally and independently to electron pairs being split with a fidelity of 90%. For low beam splitter transmittance we further find evidence of pair bunching violating statistical expectations for independent fermions

Discovery of a dysprosium metallocene single-molecule magnet with two high-temperature Orbach processes

Magnetic bistability in single-molecule magnets (SMMs) is a potential basis for new types of nanoscale information storage material. The standard model for thermally activated relaxation of the magnetization in SMMs is based on the occurrence of a single Orbach process. Here, we show that incorporating a phosphorus atom into the framework of the dysprosium metallocene [(CpiPr5)Dy(CpPEt4)]+[B(C6F5)4]- (CpiPr5 is penta-isopropylcyclopentadienyl, CpPEt4 is tetraethylphospholyl) leads to the occurrence of two distinct high-temperature Orbach processes, with energy barriers of 1410(10) and 747(7) cm-1, respectively. These barriers provide experimental evidence for two different spin-phonon coupling regimes, which we explain with the aid of ab initio calculations. The strong and highly axial crystal field in this SMM also allows magnetic hysteresis to be observed up to 70 K, using a scan rate of 25 Oe s-1. In characterizing this SMM, we show that a conventional Debye model and consideration of rotational contributions to the spin-phonon interaction are insufficient to explain the observed phenomena

An approach to understanding hydrologic connectivity on the hillslope and the implications for nutrient transport

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94780/1/gbc975.pd

Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise

Background: Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. Methods: 105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. Results: The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001). VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001). The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001). We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. Conclusions: VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter

Perceived motion in structure from motion: Pointing responses to the axis of rotation

We investigated the ability to match finger orientation to the direction of the axis of rotation in structure-from-motion displays. Preliminary experiments verified that subjects could accurately use the index finger to report direction. The remainder of the experiments studied the perception of the axis of rotation from full rotations of a group of discrete points, the profiles of a rotating ellipsoid, and two views of a group of discrete points. Subjects' responses were analyzed by decomposing the pointing responses into their slant and tilt components. Overall, the results indicated that subjects were sensitive to both slant and tilt. However, when the axis of rotation was near the viewing direction, subjects had difficulty reporting tilt with profiles and two views and showed a large bias in their slant judgments with two views and full rotations. These results are not entirely consistent with theoretical predictions. The results, particularly for two views, suggest that additional constraints are used by humans in the recovery of structure from motion