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A molecular spring for vision.

Light absorption by the visual pigment rhodopsin leads to vision via a complex signal transduction pathway that is initiated by the ultrafast and highly efficient photoreaction of its chromophore, the retinal protonated Schiff base (RPSB). Here, we investigate this reaction in real time by means of unrestrained molecular dynamics simulations of the protein in a membrane mimetic environment, treating the chromophore at the density functional theory level. We demonstrate that a highly strained all-trans RPSB is formed starting from the 11-cis configuration (dark state) within approximately 100 fs by a minor rearrangement of the nuclei under preservation of the saltbridge with Glu113 and virtually no deformation of the binding pocket. Hence, the initial step of vision can be understood as the compression of a molecular spring by a minor change of the nuclear coordinates. This spring can then release its strain by altering the protein environment.

Algorithms↗

Spatial updating relies on an egocentric representation of space: effects of the number of objects.

Models of spatial updating attempt to explain how representations of spatial relationships between the actor and objects in the environment change as the actor moves. In allocentric models, object locations are encoded in an external reference frame, and only the actor's position and orientation in that reference frame need to be updated. Thus, spatial updating should be independent of the number of objects in the environment (set size). In egocentric updating models, object locations are encoded relative to the actor, so the location of each object relative to the actor must be updated as the actor moves. Thus, spatial updating efficiency should depend on set size. We examined which model better accounts for human spatial updating by having people reconstruct the locations of varying numbers of virtual objects either from the original study position or from a changed viewing position. In consistency with the egocentric updating model, object localization following a viewpoint change was affected by the number of objects in the environment.

Environment↗

Virtual reality and medicine--from the cockpit to the operating room: are we there yet?

Teaching medicine to medical students, physicians in training and nurses is a challenging task that has remained unchanged for decades. The airline industry has achieved a great deal of safety and quality in a technically challenging environment. Many believe that their outstanding achievement is due to team training and crew resource management using simulators and dedicated training programs. Many experts in the medical profession believe that adopting the same strategies in teaching medical students and trainees could achieve significant reductions in medical errors and improve the quality of patient care. This article explores the role of teaching medicine using virtual reality in a multitude of medical specialties and outlines the use of simulation training at Saint Louis University.

Education, Medical↗

Remote sensing of coral reefs and their physical environment.

There has been a vast improvement in access to remotely sensed data in just a few recent years. This revolution of information is the result of heavy investment in new technology by governments and industry, rapid developments in computing power and storage, and easy dissemination of data over the internet. Today, remotely sensed data are available to virtually anyone with a desktop computer. Here, we review the status of one of the most popular areas of marine remote sensing research: coral reefs. Previous reviews have focused on the ability of remote sensing to map the structure and habitat composition of coral reefs, but have neglected to consider the physical environment in which reefs occur. We provide a holistic review of what can, might, and cannot be mapped using remote sensing at this time. We cover aspects of reef structure and health but also discuss the diversity of physical environmental data such as temperature, winds, solar radiation and water quality. There have been numerous recent advances in the remote sensing of reefs and we hope that this paper enhances awareness of the diverse data sources available, and helps practitioners identify realistic objectives for remote sensing in coral reef areas.

Animals↗

Advanced modeling environment for developing and testing FES control systems.

Realistic models of neuromusculoskeletal systems can provide a safe and convenient environment for the design and evaluation of controllers for functional electrical stimulation (FES) prior to clinical trials. We have developed a set of integrated musculoskeletal modeling tools to facilitate the model building process. Simulink models of musculoskeletal systems are created using two software packages developed in our laboratory, Musculoskeletal Modeling in Simulink (MMS) and virtual muscle, in addition to one software package available commercially, SIMM (Musculographics Inc., USA). MMS converts anatomically accurate musculoskeletal models generated by SIMM into Simulink(R) blocks. It also removes run-time constraints on kinetic simulations in SIMM, and allows the development of complex musculoskeletal models without writing a line of code. Virtual muscle builds realistic Simulink models of muscles responding to either natural recruitment or FES. Models of sensorimotor control systems can be developed using various Matlab (Mathworks Inc., USA) toolboxes and integrated easily with these musculoskeletal blocks in the graphical environment of Simulink.

Computer Simulation↗

Cutaneous malignant melanoma: epidemiological considerations.

Large geographic and ethnic variations in incidence and mortality rates of cutaneous malignant melanoma (CMM) suggest inverse correlations with the degree of skin pigmentation and latitude. Increases in CMM incidence and mortality rates have occurred in virtually all white populations, more markedly in those that permanently (immigrants) or temporarily (tourists/vacationers) reside in very sunny areas outside their primitive living environment. The interpretation of data from case-control studies is, however, hampered by the difficulties in quantifying retrospectively, but reliably, CMM risk correlates (e.g., host factors, sun exposure, clothing habits, sunburns) in various periods during the life span. There is, thus, a need for large prospective studies on the development of CMM and naevi, ideally in different contexts as concerns host factors, sun exposure, and other life-style habits within and across different populations.

Case-Control Studies↗

Pathogenic enterococci: new developments in the 21st century.

Enterococci, traditionally viewed as Gram-positive commensal bacteria inhabiting the alimentary canals of humans and animals, are now acknowledged to be organisms capable of causing life-threatening infections in humans, especially in the nosocomial environment. The existence of enterococci in such a dual role is facilitated, at least in part, by its intrinsic and acquired resistance to virtually all antibiotics currently in use. Beginning with the initial identification of a 'streptococci of fecal origin' in the late 19th century, enterococci have been studied for over a century now. A number of comprehensive reviews during this time have addressed various aspects of enterococci, including classification, biology, virulence, antibiotic resistance and so on. This review specifically addresses the important advances in the field of enterococcal research that have occurred since the beginning of the 21st century. Most notable among these developments have been the insights into enterococcal genomes and pathogenicity.

Adhesins, Bacterial↗

Tangible interfaces for structural molecular biology.

The evolving technology of computer autofabrication makes it possible to produce physical models for complex biological molecules and assemblies. Augmented reality has recently developed as a computer interface technology that enables the mixing of real-world objects and computer-generated graphics. We report an application that demonstrates the use of autofabricated tangible models and augmented reality for research and communication in molecular biology. We have extended our molecular modeling environment, PMV, to support the fabrication of a wide variety of physical molecular models, and have adapted an augmented reality system to allow virtual 3D representations to be overlaid onto the tangible molecular models. Users can easily change the overlaid information, switching between different representations of the molecule, displays of molecular properties, or dynamic information. The physical models provide a powerful, intuitive interface for manipulating the computer models, streamlining the interface between human intent, the physical model, and the computational activity.

Computer-Aided Design↗

Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters.

A comparison of platinum-group element (PGE) emission between gasoline and diesel engine catalytic converters is reported within this work. Whole raw exhaust fumes from four catalysts of three different types were examined during their useful lifetime, from fresh to 80,000 km. Two were gasoline engine catalysts (Pt-Pd-Rh and Pd-Rh), while the other two were diesel engine catalysts (Pt). Samples were collected following the 91441 EUDC driving cycle for light-duty vehicle testing, and the sample collection device used allowed differentiation between the particulate and soluble fractions, the latter being the most relevant from an environmental point of view. Analyses were performed by inductively coupled plasma-mass spectrometry (ICP-MS) (quadrupole and high resolution), and special attention was paid to the control of spectral interference, especially in the case of Pd and Rh. The results obtained show that, for fresh catalysts, the release of particulate PGE through car exhaust fumes does not follow any particular trend, with a wide range (one-two orders of magnitude) for the content of noble metals emitted. The samples collected from 30,000-80,000 km present a more homogeneous PGE release for all catalysts studied. A decrease of approximately one order of magnitude is observed with respect to the release from fresh catalysts, except in the case of the diesel engine catalyst, for which PGE emission continued to be higher than in the case of gasoline engines. The fraction of soluble PGE was found to represent less than 10% of the total amount released from fresh catalysts. For aged catalysts, the figures are significantly higher, especially for Pd and Rh. Particulate PGE can be considered as virtually biologically inert, while soluble PGE forms can represent an environmental risk due to their bioavailability, which leads them to accumulate in the environment.

Air Pollutants↗

A method for recording behavior and multineuronal CNS activity from tethered insects flying in virtual space.

We describe a low cost, novel virtual reality-based insect flight simulator that combines visual, olfactory and mechanosensory stimuli with multichannel neurophysiological recording techniques. Three-dimensional visual environments were created using customized modifications of a first person flight simulator computer game. Experiments could be performed in open-loop, where the flying insect's movement through the environment is 'driven' by the human operator, or in closed-loop where the movement of the environment is controlled by optically sensed movements of the insect's abdomen. During flight, we recorded multineuronal activity from the ventral nerve cord between the brain and thoracic ganglia. Results show that in open-loop conditions, induced turns of the environment evoked characteristic compensatory optomotor responses. Coordination of wing and body kinematics was similar to that observed in free flight. In closed-loop conditions, the insect was able to navigate through the simulated environment and produce flight tracks in response to presentation of pheromone that resemble those observed in free flight. We discuss the effectiveness of this preparation and its utility for addressing specific questions of insect flight as well as general questions in neuroethology.

Animals↗

A2a adenosine receptors: guanine nucleotide derivative regulation in porcine striatal membranes and digitonin soluble fraction.

We report the characterization of A2a adenosine receptors (A2aARs) in porcine striatal membranes and their solubilization (25%) by the detergent digitonin. After solubilization, the drug specificity and equilibrium [3H]CGS-21680 ([3H]2-(4-(2-carboxyethyl)phenylethylamino)-5'-N-ethyl-carboxamido -adenosine) binding parameters were virtually identical to those obtained in intact membranes, indicating a conservation of the binding site after the removal of receptors from their lipid environment. Gel filtration on a calibrated Superdex 200 HR column revealed a main [3H]CGS-21680 binding peak with an apparent molecular weight of 171,000+/-9000 Da. In membranes, Scatchard analysis of saturation data carried out in a wide range of radioligand concentration (1-100 nM) resulted in a biphasic curve and, in accordance with the two binding sites model, yielded a Kd1 = 7.4+/-0.5 and Kd2 = 53.1+/-3.6 nM, a Bmax1 = 186+/-15 fmol/mg protein and a Bmax2 = 285+/-20 fmol/mg protein, respectively. In the presence of guanosine-5'-O-(3-thiotriphosphate) (GTPgamma[S]) a shift from two affinity states to a single one was evidenced (Kd = 28.5+/-5.9 nM) and a Bmax value of 504+/-10 fmol/mg protein found. In the soluble extract, only one high-affinity state was detected (Kd = 19.3+/-1.1 nM and Bmax = 285+/-20 fmol/mg protein) and, in the presence of GTPgamma[S]), a two site model likewise provided a significantly (P < 0.01) better fit (Kd1 = 13.9+/-1.2 nM and Kd2 = 72.1+/-6.9 nM, Bmax1 = 125+/-10 fmol/mg protein and Bmax2 = 375+/-19 fmol/mg protein, respectively). These results suggest a close relation between the receptor and G protein solubilized as a functional unit and open the way to its purification.

Adenosine↗

Plants in space.

Virtually all scenarios for the long-term habitation of spacecraft and other extraterrestrial structures involve plants as important parts of the contained environment that would support humans. Recent experiments have identified several effects of spaceflight on plants that will need to be more fully understood before plant-based life support can become a reality. The International Space Station (ISS) is the focus for the newest phase of space-based research, which should solve some of the mysteries of how spaceflight affects plant growth. Research carried out on the ISS and in the proposed terrestrial facility for Advanced Life Support testing will bring the requirements for establishing extraterrestrial plant-based life support systems into clearer focus.

Adaptation, Physiological↗

Radioligand receptor assay for 25-hydroxyvitamin D2/D3 and 1 alpha, 25-dihydroxyvitamin D2/D3.

A competitive protein binding assay for measurement of the plasma concentration of 1 alpha, 25-dihydroxyvitamin D3 [1alpha, 25-(OH)2D3] has been extended to include the immediate precursor of this hormone, 25-hydroxyvitamin D3 (25-OHD3). In addition, the assay system is capable of measuring the two metabolic products of ergocalciferol, namely. 25-hydroxyvitamin D2 (25-OHD2) and 1alpha, 25-dihydroxyvitamin D2 [1alpha, 25-(OH)2D2]. The target tissue assay system consists of a high affinity cytosol receptor protein that binds the vitamin D metabolites and a limited number of acceptor sites on the nuclear chromatin. By utilizing a series of chromatographic purification steps, a single plasma sample can be assayed for any of the four vitamin D metabolites either individually or combined. Therefore, the assay procedure allows for both the quantitative and qualitative assessment of the total active vitamin D level in a given plasma sample. To show that the binding assay was capable of measuring 1alpha, 25-(OH)2D2 as well as 1alpha, 25 (OH)2D3, two groups of rats were raised. One group, supplemented with vitamin D3, produced assayable material that represented 1alpha, 25-(OH)2D3. The other group, fed only vitamin D2 in the diet, yielded plasma containing only 1alpha, 25-(OH)2D2 as the hormonal form of the vitamin. The circulating concentrations of the two active sterols were nearly identical (15 ng/100 ml) in both groups, indicating that the competitive binding assay can be used to measure both hormonal forms in plasma. In a separate experiment, 1alpha, 25-(OH)2D2 was generated in an in vitro kidney homogenate system using 25-OHD2 as substrate. Comparison of this sterol with 1alpha, 25-(OH)2D3 in the assay system showed very similar binding curves; the D2 form was slightly less efficient (77%). Comparison of the respective 25-hydroxy forms (25-OHD2 vs. 25-OHD3) at concentrations 500-fold that of 1alpha, 25-(OH)2D3, again suggested that the binding of the D2 metabolite was slightly less efficient (71%). Finally, the assay was employed to measure the total active vitamin D metabolite pools in the plasma of normal subjects and patients with varying degrees of hypervitaminosis D. The normal plasma levels of 25-OHD and 1alpha, 25-(OH)2D measured in Tucson adults were 25-40 ng/ml and 2.1-4.5 ng/100 ml, respectively. Both sterols were predominately (greater than 90%) in the form of vitamin D3 metabolites in this environment. Typical cases of hypervitaminosis D exhibited approximately a 15-fold increase in the plasma 25-OHD concentration, and a dramatic changeover to virtually all metabolites existing in the form of D2 vitamins. In contrast, the circulating concentration of 1alpha, 25-(OH)2D was not substantially enhanced in vitamin D-intoxicated patients. We therefore conclude that hypervitaminosis D is not a result of abnormal plasma levels of 1alpha, 25-(OH)2D but may be cuased by an excessive circulating concentration of 25-OHD.

Animals↗

Applications of virtual reality technology in pathology.

TelePath(SM) a telerobotic system utilizing virtual microscope concepts based on high quality still digital imaging and aimed at real-time support for surgery by remote diagnosis of frozen sections. Many hospitals and clinics have an application for the remote practice of pathology, particularly in the area of reading frozen sections in support of surgery, commonly called anatomic pathology. The goal is to project the expertise of the pathologist into the remote setting by giving the pathologist access to the microscope slides with an image quality and human interface comparable to what the pathologist would experience at a real rather than a virtual microscope. A working prototype of a virtual microscope has been defined and constructed which has the needed performance in both the image quality and human interface areas for a pathologist to work remotely. This is accomplished through the use of telerobotics and an image quality which provides the virtual microscope the same diagnostic capabilities as a real microscope. The examination of frozen sections is performed a two-dimensional world. The remote pathologist is in a virtual world with the same capabilities as a "real" microscope, but response times may be slower depending on the specific computing and telecommunication environments. The TelePath system has capabilities far beyond a normal biological microscope, such as the ability to create a low power image of the entire sample using multiple images digitally matched together; the ability to digitally retrace a viewing trajectory; and the ability to archive images using CD ROM and other mass storage devices.

Alabama↗

The topography of glycerophosphate acyltransferase in the transverse plane of the mitochondrial outer membrane.

In low ionic media, mitochondrial glycerophosphate acyltransferase was inhibited virtually completely within 15 min by the nonspecific proteases, proteinase K and subtilisin. In high ionic media, the mitochondrial enzyme was either not inhibited or was marginally inhibited by these proteases. Chymotrypsin and trypsin, regardless of the ionic strength of the medium, did not inhibit the acyltransferase. Substantial inhibition by proteinase K and subtilisin was observed in the high ionic media when the incubation was continued for 30 or 45 min. Adenylate kinase, an intermembrane enzyme, was not inhibited under any of the above conditions. These results demonstrate a cytosolic exposure of the mitochondrial acyltransferase. In a low ionic environment, when the outer membrane integrity was damaged either by gradually decreasing the tonicity of the medium or by stepwise addition of Triton X-100, either chymotrypsin or trypsin caused virtually parallel inhibition of glycerophosphate acyltransferase and adenylate kinase. A more direct approach in establishing the existence of protease-susceptible sites on the inner side of the outer membrane was taken by observing the inhibition of mitochondrial glycerophosphate acyltransferase and adenylate kinase in trypsinloaded right-side-out outer membrane vesicles incubated in the presence of externally located soybean trypsin inhibitor. The above results, taken together, suggest that mitochondrial glycerophosphate acyltransferase spans the transverse plane of the outer membrane.

Acyltransferases↗

Auditory localization under sustained +Gz acceleration.

The ability to localize a virtual sound source in the horizontal plane was evaluated under varying levels of sustained (+Gz) acceleration. Participants were required to judge the locations of spatialized noise bursts in the horizontal plane (elevation 0 degrees) during exposure to 1.0, 1.5, 2.5, 4.0, 5.5, and 7.0 +Gz. The experiment was conducted at the U.S. Air Force Research Laboratory's Dynamic Environment Simulator, a three-axis centrifuge. No significant increases in localization error were found between 1.0 and 5.5 +Gz; however, a significant increase did occur at the 7.0 +Gz level. In addition, the percentage of front/back confusions did not vary as a function of +Gz level. Collectively, these results indicate that the ability to localize virtual sound sources is well maintained at various levels of sustained acceleration. Actual or potential applications include the incorporation of spatial audio displays into the human-computer interface for vehicles that are operated in acceleration environments.

Acceleration↗

The human hippocampus and spatial and episodic memory.

Finding one's way around an environment and remembering the events that occur within it are crucial cognitive abilities that have been linked to the hippocampus and medial temporal lobes. Our review of neuropsychological, behavioral, and neuroimaging studies of human hippocampal involvement in spatial memory concentrates on three important concepts in this field: spatial frameworks, dimensionality, and orientation and self-motion. We also compare variation in hippocampal structure and function across and within species. We discuss how its spatial role relates to its accepted role in episodic memory. Five related studies use virtual reality to examine these two types of memory in ecologically valid situations. While processing of spatial scenes involves the parahippocampus, the right hippocampus appears particularly involved in memory for locations within an environment, with the left hippocampus more involved in context-dependent episodic or autobiographical memory.

Animals↗

Degenerate hearing and sound localization in naked mole rats (Heterocephalus glaber), with an overview of central auditory structures.

Behavioral tests of absolute sensitivity and sound localization in African naked mole rats show that, despite their communal social structure and large vocal repertoire, their hearing has degenerated much like that of other subterranean species. First, their ability to detect sound is limited, with their maximum sensitivity being only 35 dB (occurring at 4 kHz). Second, their high-frequency hearing is severely limited, with their hearing range (at 60 dB sound pressure level [SPL]) extending from 65 Hz to only 12.8 kHz. Third, determination of the effect of duration on noise thresholds indicates that, compared with other animals, mole rats require a sound to be present for a much longer duration before reaching asymptotic threshold. Finally, they are unable consistently to localize sounds shorter than 400 ms and cannot accurately localize sounds of longer duration, raising the possibility that they are unable to use binaural locus cues. Thus, it seems that the essentially one-dimensional burrow system of a subterranean habitat produces severe changes in hearing comparable to the changes in vision that result from the absence of light. To explore the relation between vision and sound-localization acuity, retinal ganglion cell densities were determined. The results indicate that naked mole rats have a broad area of best (albeit poor) vision, with maximum acuity estimated at 44 cycles/degree. That mammals with wide fields of best vision have poorer sound-localization acuity than those with narrower fields is consistent with the thesis that a major function of sound localization is to direct the gaze to the source of a sound. However, the fact that subterranean mammals have little use for vision in a lightless environment suggests that they represent an extreme case in this relationship and may explain the fact that, unlike surface-dwelling mammals, they have virtually lost the ability to localize brief sounds. Finally, despite their very limited auditory abilities, the major brainstem auditory nuclei, although relatively small, appear to be present.

Animals↗