Involvement of annexin V in the entry of influenza viruses and role of phospholipids in infection.

Influenza viruses bind to annexin V, a widely spread non-glycosylated phospholipid-binding protein. Externally added phospholipids as well as antiserum against this protein specifically inhibit infection of these viruses in cell cultures. We conclude that annexin V plays an important role in the entry of these viruses.

Dominance of memory over naive T cells in contact dermatitis is due to differential tissue immigration.

CD4+ T cells include a naive (CD4-, CD45RO-, CD29-, CD45RA+) as well as a memory subpopulation (CD4+, CD45RO+, CD29+, CD45RA-). These subpopulations represent different stages in T-cell development and function. Recently, it has been shown that inflammatory and neoplastic CD4+ T-cell infiltrates are dominated by the memory subpopulation, whereas both subpopulations are about the same size in the peripheral blood. This was thought to be the result of in situ maturation of naive into memory T cells. We analysed early positive patch-test reactions 1-2 days after antigen challenge and found that most of the CD4+ T cells that had freshly immigrated into the tissue carried the memory phenotype. Their preferential migration may be mediated by at least five adhesion molecules expressed on their cell surface. This observation has important pathogenetic implications, since memory T cells can be rapidly activated by antigens and secrete a wide variety of pro-inflammatory cytokines.

Tau protein becomes long and stiff upon phosphorylation: correlation between paracrystalline structure and degree of phosphorylation.

In a previous report we have shown that microtubule-associated protein tau can be induced to form paracrystals (Lichtenberg, B., E.-M. Mandelkow, T. Hagestedt, and E. Mandelkow. 1988. Nature [Lond.]. 334:359-362). A striking feature was the high degree of elasticity of the molecules. We now report that this property is related to the state of phosphorylation. When tau is dephosphorylated by alkaline phosphatase, it becomes shorter and more elastic; when it is phosphorylated by Ca++/calmodulin-dependent kinase, it becomes longer and stiffer. This may provide a model for the control of structural properties of tau-like molecules by phosphorylation.

Structure and elasticity of microtubule-associated protein tau.

Tau is one of the diverse group of microtubule-associated proteins that bind to microtubules and may thereby influence their structure and function. It occurs in the mammalian brain, mainly in axons, and is a component of the neurofibrillary tangles of Alzheimer's disease. Tau was recently sequenced, but there remains a short-age of structural data on the protein. We have now prepared paracrystals of tau suitable for electron microscopy and image processing. They show distinct transverse banding and polarity, indicating that the protein subunits are aligned with the same orientations. In contrast to other paracrystals, those of tau protein can stretch or contract continuously by more than three-fold; the axial repeats range from 22 to 68 nm. After scaling to a common period, the density distributions are closely superimposable. This suggests that tau is an elastic molecule.

Vestibular factors influencing the biomedical support of humans in space.

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 1. Sensory adaptation to weightlessness and readaptation to one-g: an overview.

Experiments on human spatial orientation were conducted on four crewmembers of Space Shuttle Spacelab Mission 1. This introductory paper presents the conceptual background of the project, the relationship among the experiments and their relevance to a "sensory reinterpretation hypothesis". Detailed experiment procedures and results are presented in the accompanying papers in this series. The overall findings are discussed in this article as they pertain to the following aspects of hypothesized sensory reinterpretation in weightlessness: utricular otolith afferent signals are reinterpreted as indicating head translation rather than tilt, sensitivity of reflex responses to footward acceleration is reduced, and increased weighting is given to visual and tactile cues in orientation perception and posture control. Three subjects developed space motion sickness symptoms, which abated after several days. Head movements, as well as visual and tactile cues to orientation influenced symptoms in a manner consistent with the sensory-motor conflict theory of space motion sickness. Six short duration tests of motion sickness susceptibility, conducted pre-flight, failed to predict sickness intensity in weightlessness. An early otolith-spinal reflex, measured by electromyography from the gastrocnemius-soleus muscles during sudden footward acceleration, was inhibited immediately upon entering weightlessness and declined further during the flight, but was unchanged from pre-flight when measured shortly after return to earth. Dynamic visual-vestibular interaction was studied by measuring subjective roll self-motion created by looking into a spinning drum. Results suggest increased weighting of visual cues and reduced weighting of graviceptor signals in weightlessness. Following the 10 day flight, erect posture with eyes closed was disturbed for several days.(ABSTRACT TRUNCATED AT 250 WORDS)

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 4. Space motion sickness: symptoms, stimuli, and predictability.

Space sickness symptoms were observed by 4 specially trained observers on Spacelab-1. Three reported persistent symptoms, and vomited repeatedly during the first and/or second day of flight. Head movements on all axes were provocative, particularly in pitch and roll. Head acceleration data recorded from 2 symptomatic crewmen showed that after several hours of physical activity in orbit, symptoms appeared, and thereafter both crewmen were compelled to limit head movements. Firm body contact with motionless surfaces helped alleviate symptoms. When crewmembers floated into unfamiliar body orientations in the cabin, inherent ambiguities in static visual orientation cues sometimes produced spatial reorientation episodes which were also provocative. Symptoms largely resembled those of other forms of prolonged motion sickness, superimposed upon other symptoms attributable to fluid shift. All 4 eventually used anti-motion sickness drugs. When they did, vomiting frequency was reduced. By the 4th day, symptoms subsided, and head accelerations again increased in magnitude and variability. Sickness intensity in orbit was not predicted by statistically concordant results of 6 acute preflight susceptibility tests. However, results from a longer duration preflight prism goggles test showed an apparent correlation. All subjects were asymptomatic making head movements in parabolic flight 4 days after the mission, but not 1 year later. Overall, results support the view that space sickness is a motion sickness.

Otolith tilt-translation reinterpretation following prolonged weightlessness: implications for preflight training.

Observations with three astronauts yielded two major findings. First, perceived self-motion during sinusoidal roll differed immediately postflight from preflight. Between 70 and 150 min after landing, roll was perceived primarily as linear translation. Secondly, more horizontal eye movement was elicited by roll stimulation immediately postflight relative to both preflight and later postflight observations. These results support an "otolith tilt-translation reinterpretation" hypothesis, which has clear implications for understanding astronaut reports of space motion sickness during the early period of orbital flight. A proposal for "prophylactic adaptation training" which may provide preflight adaptation to weightlessness, derives from this research.

Spatial orientation in weightlessness and readaptation to earth's gravity.

Unusual vestibular responses to head movements in weightlessness may produce spatial orientation illusions and symptoms of space motion sickness. An integrated set of experiments was performed during Spacelab 1, as well as before and after the flight, to evaluate responses mediated by the otolith organs and semicircular canals. A variety of measurements were used, including eye movements, postural control, perception of orientation, and susceptibility to space sickness.

Payload crew members' view of spacelab operations.

Various operational aspects of the Spacelab 1 mission are reviewed by the four payload crew members. Two-shift operations, voice communication with ground investigators, joint participation in experiment activity, Spacelab performance, and recent advances are discussed.

Effects of recB, recF and uvrA mutations on Weigle reactivation of lambda phages in Escherichia coli K12 treated with 8-methoxypsoralen or angelicin and 365-nm light.

The extent of Weigle reactivation (W-R) of lambda c+ phages treated with bifunctional 8-methoxypsoralen and 365-nm light (8-MOP + UVA) and with monofunctional angelicin and 365-nm light (ANG + UVA) were compared in Escherichia coli strains with different excision repair and recombinational capacities. In uvrA6 host cells, irradiation of the cells with 254-nm radiation only decreased the survival of phages treated with 8-MOP + UVA. The extent of W-R of ANG + UVA-treated phages in uvrA6 cells, however, was much larger than that obtained in other host cells. These results indicate that monoadducts produced by ANG + UVA treatment can be repaired effectively by the repair induced without uvrA gene products, but lesions produced by 8-MOP + UVA treatment cannot be repaired by the repair. The small W-R of ANG + UVA-treated phages in wild-type cells may be due to the high repairability of the lesions by constitutive excision repair in the cells. recB21 reduced only a little of the W-R of 8-MOP + UVA- or ANG + UVA-treated phages obtained in wild-type cells. Although recF143 cells have an almost comparable host-cell repair capacity of 8-MOP + UVA- or ANG + UVA-treated phages to that of the wild-type cells, recF143 mutation reduced not only the extent of W-R of 8-MOP + UVA-treated phages to 17% of that obtained in wild-type cells but also the extent of W-R of ANG + UVA-treated phages to 12% of that obtained in uvrA6 cells.

Human ocular counterrolling induced by varying linear accelerations.

Ocular counterrolling (OCR) has previously been studied using static head tilt or continuous rotation about the line of sight as a stimulus to the otolith organs. This study presents the first measurements of OCR in humans induced by linear accelerations. Dynamic measurements of the response to lateral linear acceleration indicate the eye movements to be on the order of 2 degrees for 0.2 g peak acceleration, 0.2 Hz sinusoidal acceleration. These values are consistent with static OCR studies. The dynamics of the response are similar to a low order linear system with a dominant time constant of 0.33 s. A previous model predicts a time constant of 0.32 s. Sinusoidal oscillation at 0.2, 0.4, and 1.0 Hz with a 0.2 g peak acceleration showed good agreement with the model in both gain and phase. The question of amplitude linearity remains unsettled. This otolithocular reflex, over short periods at least, appears to be stationary in the statistical sense.

Ocular torsion on earth and in weightlessness.

Ocular torsion (OT) was measured in human subjects during horizontal linear acceleration on a sled in the laboratory and when emerging from weightlessness during parabolic flights in NASA's KC-135 aircraft. Analysis of the frequency response of OT to sinusoidal horizontal oscillation on earth shows results consistent with constant tilt rate studies and with earlier models based on perception of acceleration. Step responses of OT to lateral acceleration are compared to similar profiles from aircraft tests with no preexisting gravitoinertial force on the otoliths. The sensitivity of OT to rotating wide fields producing vection and to tactile cues is compared for earth and weightlessness. A new instrument for high bandwidth video measurement of OT using a soft-contact-lens target is described.