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PubMed2004

Human posterior auditory cortex gates novel sounds to consciousness.

Life or death in hostile environments depends crucially on one's ability to detect and gate novel sounds to awareness, such as that of a twig cracking under the paw of a stalking predator in a noisy jungle. Two distinct auditory cortex processes have been thought to underlie this phenomenon: (i) attenuation of the so-called N1 response with repeated stimulation and (ii) elicitation of a mismatch negativity response (MMN) by changes in repetitive aspects of auditory stimulation. This division has been based on previous studies suggesting that, unlike for the N1, repetitive "standard" stimuli preceding a physically different "novel" stimulus constitute a prerequisite to MMN elicitation, and that the source loci of MMN and N1 are different. Contradicting these findings, our combined electromagnetic, hemodynamic, and psychophysical data indicate that the MMN is generated as a result of differential adaptation of anterior and posterior auditory cortex N1 sources by preceding auditory stimulation. Early ( approximately 85 ms) neural activity within posterior auditory cortex is adapted as sound novelty decreases. This alters the center of gravity of electromagnetic N1 source activity, creating an illusory difference between N1 and MMN source loci when estimated by using equivalent current dipole fits. Further, our electroencephalography data show a robust MMN after a single standard event when the interval between two consecutive novel sounds is kept invariant. Our converging findings suggest that transient adaptation of feature-specific neurons within human posterior auditory cortex filters superfluous sounds from entering one's awareness.

Adult↗

PubMed2004

Overexpression of OsRAA1 causes pleiotropic phenotypes in transgenic rice plants, including altered leaf, flower, and root development and root response to gravity.

There are very few root genes that have been described in rice as a monocotyledonous model plant so far. Here, the OsRAA1 (Oryza sativa Root Architecture Associated 1) gene has been characterized molecularly. OsRAA1 encodes a 12.0-kD protein that has 58% homology to the AtFPF1 (Flowering Promoting Factor 1) in Arabidopsis, which has not been reported as modulating root development yet. Data of in situ hybridization and OsRAA1::GUS transgenic plant showed that OsRAA1 expressed specifically in the apical meristem, the elongation zone of root tip, steles of the branch zone, and the young lateral root. Constitutive expression of OsRAA1 under the control of maize (Zea mays) ubiquitin promoter resulted in phenotypes of reduced growth of primary root, increased number of adventitious roots and helix primary root, and delayed gravitropic response of roots in seedlings of rice (Oryza sativa), which are similar to the phenotypes of the wild-type plant treated with auxin. With overexpression of OsRAA1, initiation and growth of adventitious root were more sensitive to treatment of auxin than those of the control plants, while their responses to 9-hydroxyfluorene-9-carboxylic acid in both transgenic line and wild type showed similar results. OsRAA1 constitutive expression also caused longer leaves and sterile florets at the last stage of plant development. Analysis of northern blot and GUS activity staining of OsRAA1::GUS transgenic plants demonstrated that the OsRAA1 expression was induced by auxin. At the same time, overexpression of OsRAA1 also caused endogenous indole-3-acetic acid to increase. These data suggested that OsRAA1 as a new gene functions in the development of rice root systems, which are mediated by auxin. A positive feedback regulation mechanism of OsRAA1 to indole-3-acetic acid metabolism may be involved in rice root development in nature.

Amino Acid Sequence↗

PubMed1997

Efficacy of two commercial products for altering urine drug test results.

OBJECTIVE: We have become aware of several commercial products that, when orally ingested, will purportedly not only eliminate "toxins" from a person's system, but will also correct any urinary imbalances caused by excessive water consumption. METHOD: Unblinded study of one volunteer subject, tested weekly x 4 for 24-hour urine elimination of test drug under conditions of control, control plus 1200 mL water, Quick Flush', and Eliminator. RESULTS: Each of the treatment protocols studied caused reductions of drug or metabolite concentrations as measured by gas chromatography-mass spectrometry in urine specimens collected up to 24 hours after ingestion of amphetamine, 9-carboxy-11-nor-delta-9-THC, benzoylecgonine, or codeine, yet the radioimmunoassay screening results demonstrated very little effect. Water alone was approximately as effective as the two commercial products in reducing the metabolite level. None of the treatment protocols employed in this study altered urinary pH, specific gravity, or creatinine concentration outside the normally accepted physiological range. CONCLUSIONS: Attempts to conceal drug abuse by water dilution are most likely to play a substantial role when concentrations are at or near the detection threshold for a particular assay such as the terminal stages of drug eliminations.

Amphetamine↗

PubMed1992

Collagen in organ development.

It is important to know whether microgravity will adversely affect developmental processes. Collagens are macromolecular structural components of the extracellular matrix (ECM) which may be altered by perturbations in gravity. Interstitial collagens have been shown to be necessary for normal growth and morphogenesis in some embryonic organs, and in the mouse salivary gland, the biosynthetic pattern of these molecules changes during development. Determination of the effects of microgravity on epithelial organ development must be preceded by crucial ground-based studies. These will define control of normal synthesis, secretion, and deposition of ECM macromolecules and the relationship of these processes to morphogenesis.

Animals↗

PubMed1999

[Errors in pointing under various body orientation relative to the gravity vector].

Errors in pointing to remembered target locations were measured in healthy subjects in upright, supine and prone positions, i.e. in three positions differing in body and arm movement orientation relative to the gravity vector. The X-error was unaffected by the body position, whereas the Y-error was dependent on subject's orientation relative to the gravity vector. In two lying positions, the subjects pointed below and in the vertical posture above the remembered target locations. On the contrary, the variable error was differentially affected by orientation of the movement trajectory relative to the gravity vector. In the supine position, the variable error was larger and in the prone position, smaller than in the upright posture. The gravity bias in pointing errors suggests that the motor program generated in the lying position is not modified to adapt to altered orientation relative to the gravity vector.

Adult↗

PubMed1999

Chronic toxicity and carcinogenicity studies of ethylenediamine dihydrochloride by dietary incorporation in Fischer 344 rats.

Ethylenediamine dihydrochloride (EDA.2HCl) was incorporated into the diet and fed to Fischer 344 rats for 2 years at target doses of 0, 0.02, 0.10 or 0.35 g/kg/day (equivalent to 0.009, 0.045 and 0.158 g free EDA/kg/day). Two separate untreated control groups were used. Interim sacrifices were at 6, 12 and 18 months and the terminal sacrifice was at 24 months. Under the conditions of this study, EDA.2HCl was not carcinogenic in the Fischer 344 rat. Most toxic responses were observed at the 12-month sacrifice and thereafter. Reductions in mean body weight gain were observed in high dose group male rats throughout most of the study and in the high dose group of female rats after approximately 18 months. Conversely, there was a slight increase in the mean body weight gain for the medium level female rats from about day 21 until 21 months that was of equivocal biological significance. Increased mortality was observed in the high dose group of both sexes and the mid dose group of female rats. The cause of the decreased survival was unclear, but may have been related to the enhancement of background degenerative lesions such as chronic nephropathy. Throughout the study, male rats from the high dose group had decreased erythrocyte counts, haemoglobin concentration and haematocrit. The cause and biological significance of the haematological changes were unknown. Increased water consumption was observed in the high dose group of both sexes during the latter half of the study. Increased urine volume with concurrent decreased urine specific gravity was generally observed in the high dose group of both sexes in the last half of the study and suggested a possible alteration in kidney function. Altered urine volume and specific gravity persisted to termination in female rats only. Slight increases in absolute and relative kidney weights were also observed in the high dose group of female rats during the latter half of the study. Hepatocellular pleomorphism was observed in the high dose group of both sexes, especially the female rats, and may have contributed to increased mean liver weights observed primarily in female rats from the high dose group. Hepatocellular pleomorphism was first observed in female rats at 12 months but was not observed in male rats until the final sacrifice. Rhinitis and tracheitis were observed with greater frequency in the high dose group of male rats at 12, 18 and 24 months and in high dose group female rats at 18 months. At 24 months, rhinitis, but not tracheitis, persisted at a significantly greater frequency in high dose group female rats. The apparent no-observable-effect level (NOEL) of this study was at the lowest dose level, 0.02 g/kg/day (equivalent to 9 mg EDA/kg/day).

Animals↗

PubMed1997

Effect of body orientation with respect to gravity on directional accuracy of human pointing movements.

Errors in pointing to remembered target locations were measured in normal subjects in the upright posture and in a supine or prone lying position, three conditions that differed in the orientation of the moving arm with respect to gravity. Vertical errors, or, more strictly, errors along the body axis, were significantly larger in both supine and prone lying positions as compared with the vertical posture. Subjects' orientation with respect to gravity produced a consistent error pattern, i.e. subjects pointed below the remembered target locations in the vertical posture and above them under the two lying conditions, in the body-related co-ordinates. On the contrary, variable error (the confidence ellipse) was differentially affected by the orientation of the movement trajectory with respect to gravity. In the supine body position the variable error was larger, and in the prone position it was smaller than in the upright posture. The finding of gravity-related bias in pointing errors suggests that the motor programme generated in the lying position is not modified to adapt to an altered orientation with respect to gravity.

Adult↗

PubMed1996

Muscle activity patterns altered during pedaling at different body orientations.

Gravity is a contributing force that is believed to influence strongly the control of limb movements since it affects sensory input and also contributes to task mechanics. By altering the relative contribution of gravitational force to the overall forces used to control pedaling at different body orientations, we tested the hypothesis that joint torque and muscle activation patterns would be modified to generate steady-state pedaling at altered body orientations. Eleven healthy subjects pedaled a modified ergometer at different body orientations (from horizontal to vertical), maintaining the same workload (80 J), cadence (60 rpm), and hip and knee kinematics. Pedal reaction forces and crank and pedal kinematics were measured and used to calculate joint torques and angles. EMG was recorded from four muscles (tibialis anterior, triceps surae, rectus femoris, biceps femoris). Measures of muscle activation (joint torque and EMG activity) showed strong dependence on body orientation, indicating that muscle activity is not fixed and is modified in response to altered body orientation. Simulations confirmed that, while joint torque changes were not necessary to pedal at different body orientations, observed changes were necessary to maintain consistent crank angular velocity profiles. Dependence of muscle activity on body orientation may be due to neural integration of sensory information with an internal model that includes characteristics of the endpoint, to produce consistent pedaling trajectories. Thus, both sensory consequences and mechanical aspects of gravitational forces are important determinants of locomotor tasks such as pedaling.

Adult↗

PubMed1998

Effect of low urine specific gravity on pregnancy testing.

Urine pregnancy tests performed at a large urban university student health center were examined for specific gravity to determine whether a low urine specific gravity, compared with a serum specimen, could alter the result of a urine pregnancy test. At the same time, a serum pregnancy test was performed on those samples with negative results and a specific gravity of less than 1.015. During the study period, 410 urine specimens were evaluated. Eighty of the women with a specific gravity under 1.015 had negative urine pregnancy tests with a concomitant serum specimen. The authors concluded that current sensitive immunoassay tests for human chorionic gonadotropin (HCG) are highly sensitive and that low specific gravity does not appear to alter this sensitivity.

Bias↗

PubMed2004

Exploration of small fibers for testing diabetic neuropathies.

INTRODUCTION: Electrophysiological exploration of neuropathies is a standard method of investigating the dysfunction of myelinated larger fibers (Aalpha, Abeta). However, this method cannot test dysfunctions in other fibers. To evaluate the smaller (Adelta) and unmyelinated fiber (C-fibers) lesions a quantitative method has been perfected: the study of the sensory thresholds (quantitative sensory testing: QST). It allows the investigation of the sensory symptoms and is a reproducible, non-invasive and painless method. It is used above all in patients suffering from diabetic neuropathy ('Diabetes Care 9 (1987) 432'). PATIENTS AND METHODS: We used the QST testing in comparison with nerve conduction velocities in 40 Non-Insulin-Dependent Diabetes Mellitus (NIDDM or Type II) patients in their 60s (+/-10 years). Depending on the duration of their diabetes (dd), we distinguished three groups: dd < 5 years (GI) dd from 5 to 15 years (GII) and dd > 15 years (GIII). All the patients underwent a clinical neurological examination, which enabled us to establish a gravity score comparable to the NDS (Neuropathy Disability Score: 'Muscle Nerve 10 (1988) 21'). RESULTS: Nerve conduction velocities and QST were studied for each group of patients. Electrophysiological alterations were connected to the gravity clinical score and in some asymptomatic patients a higher QST heat threshold could be observed. DISCUSSION: These results indicate that QST can detect the early dysfunction of the unmyelinated fibers in this kind of neuropathy. Subclinical detection can reduce severe neurological complications and make possible an early and effective treatment.

Aged↗

PubMed2002

Enhanced expression of the LDH-A gene after gravity-changing stress in human RSa cells.

A major issue in radiation and space biology is whether gene expression levels are altered in cells exposed to gravity-changing stress. In the present study, genes up- or down-regulated in radiation-sensitive human RSa cells cultured under gravity-changing conditions, were identified using a PCR-based mRNA differential display method. Exposure of cells to gravity-changing stress was performed by free-fall with a drop-shaft facility or by an airplane-conducted parabolic flight. Among the candidates for gravity-changing stress-responsive genes obtained by the differential display analysis, the lactate dehydrogenase A gene (LDH-A) was confirmed by Northern blotting analysis to exhibit increased expression levels. The gravity-changing stress consisted of a combination of microgravity and hypergravity. However, exposure of the cells to hypergravity produced by centrifuge only slightly affected the LDH-A mRNA expression. Thus, LDH-A was found to be a candidate for the genes which play a role in the cellular response to gravity-changing stress, and mainly to microgravity.

Cell Line↗

PubMed1992

The influence of head position and head reorientation on the axis of eye rotation and the vestibular time constant during postrotatory nystagmus.

Reorienting the head with respect to gravity during the postrotatory period alters the time course of postrotatory nystagmus (PRN), hastening its decline and thereby reducing the calculated vestibular time constant. One explanation for this phenomenon is that the head reorientation results in a corresponding reorientation of the axis of eye rotation with respect to head coordinates. This possibility was investigated in 10 human subjects whose eye movements were monitored with a three-dimensional magnetic field - search - coil technique using a variety of head reorientation paradigms in a randomized order during PRN following the termination of a 90 degrees/s rotation about earth vertical. Average eye velocities were calculated over two time intervals: from 1 s to 2 s and from 7 s to 8 s after cessation of head rotation. The time constant was estimated as one third of the duration of PRN. For most conditions, a reorientation of the head with respect to gravity 2 s after the rotation had stopped did not significantly alter the direction of the eye velocity vector of PRN with respect to head coordinates. This strongly indicates that, in humans, PRN is mainly stabilized in head coordinates and not in space coordinates, even if the otolith input changes. This finding invalidates the notion that the shortening of PRN due to reorientation of the head could be due to a change of the eye velocity vector towards a direction (torsion), which is not detectable with the eye recording methods (electrooculography) used in earlier studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1997

Microgravity reduces the differentiation of human osteoblastic MG-63 cells.

Spaceflight leads to osteopenia in both humans and animals, principally as a result of decreased bone formation, which might be the consequence of impaired osteoblast differentiation. The effect of microgravity on osteoblast differentiation in vitro was investigated using the human osteosarcoma cell line MG-63. Genes related to matrix formation and maturation were quantified both at the protein and mRNA level in untreated and hormone-treated (dihydroxyvitamin D3 [1,25(OH)2D3], 10(-7) M; transforming growth factor beta2 (TGF-beta2), 10 ng/ml) cells cultured for 9 days under microgravity conditions aboard the Foton 10 satellite and compared with ground and inflight unit-gravity cultures. The expression of alkaline phosphatase (ALP) activity following treatment at microgravity increased only by a factor of 1.8 compared with the 3.8-fold increase at unit-gravity (p < 0.01), whereas no alteration was detected in the production of collagen type I between unit- and microgravity. In addition, gene expression for collagen Ialpha1, ALP, and osteocalcin following treatment at microgravity was reduced to 51, 62, and 19%, respectively, of unit-gravity levels (p < 0.02). The lack of correlation between collagen type I gene and protein expression induced by microgravity is most likely related to the different kinetics of gene and protein expression observed at unit-gravity: following treatment with 1,25(OH)2D3 and TGF-beta2, collagen Ialpha1 mRNA increased gradually during 72 h, but collagen type I production was already maximal after treatment for 48 h. In conclusion, microgravity decreases the activity of osteoblasts in vitro; in particular the differentiation of osteoblasts in response to systemic hormones and growth factors is reduced by microgravity.

Alkaline Phosphatase↗

PubMed1979

Anaesthesia and the respiratory system.

Pulmonary gas exchange is disturbed during general anaesthesia; both oxygenation and elimination of carbon dioxide are impaired. The shape of the chest wall alters after induction of anaesthesia-paralysis in recumbent subjects, and its motion during inspiration is also altered. The mechanical properties of lung and chest wall are also affected and FRC may be reduced. Inspired gas distribution changes after induction of anaesthesia-paralysis with mechanical ventilation of the lungs. Distribution of pulmonary blood flow is altered in subjects in the sitting and right lateral decubitus positions, but the distribution is not adjusted to the altered distribution of inspired gas. This results in an increased mismatching of ventilation to perfusion, with development of lung regions that have low and high ventilation-to-perfusion ratios. Some lung regions with low ventilation-to-perfusion ratios develop into right-to-left shunt on breathing 100 per cent oxygen. The following sequence of events probably occurs after induction of anaesthesia-paralysis. The initial effect of anaesthesia seems to be on the shape and motion of the chest wall. This may alter the mechanical properties of both the chest wall and the lung. Intrapulmonary gas distribution is altered secondarily. Pulmonary bloodflow distribution, which is primarily determined by gravity, does not seem to adjust to the altered distribution of inspired gas. Hence, an increased mismatching of ventilation to perfusion develops. This includes the development of lung regions with low ventilation-to-perfusion ratios. These regions may progress into right-to-left shung during 100 per cent oxygen breathing. The low ventilation-to-perfusion regions and the shunt may both impair oxygenation. The development of lung regions with high ventilation-to-perfusion ratios after induction of anaesthesia-paralysis contributes to the inefficient elimination of carbon dioxide.

Anesthesia, General↗

PubMed2001

[Influence of gravity change on EGF-induced signal transduction].

With the development of aerospace technology, biological effects induced by alteration of gravitation are drawing more and more attention. Among them the influence of alteration of gravitation on cytokine-induced signal transduction has been well studied recently. Epidermal growth factor (EGF)-induced signal transduction can activate increase of cell proliferation in most cell types, so it is always a hotspot in these years. Among the early effects evoked by EGF are receptor clustering, cell rounding, and early gene expression. After the study about the induction of EGF on human A431 cell line, it was observed that EGF-induced c-fos and c-jun expression decreased in microgravity. This was caused by alteration of the EGF receptor and protein kinase C-mediated signal transduction pathways. Meanwhile the key component of cytoskeleton, the actin microfilament system, was found to be linked to the EGF-induced signal transduction cascades either. So it seems reasonable to suggest that the cytoskeleton constitutes the gravity-sensitive cell component.

Actin Cytoskeleton↗

PubMed1992

Experiments with suspended cells on the Space Shuttle.

Spaceflight experiments since 1981 have demonstrated that certain cell functions are altered by micro-g. Biophysical models suggest that cell membranes and organelles should not be affected directly by gravity, however, the chemical microenvironment surrounding the cell and molecular transport could be altered by reduced gravity. Most experiments have used suspended live cells in small chambers without stirring or medium exchange. Flight results include increased attachment of anchorage-dependent human cells to collagen coated microcarriers, reduced secretion of growth hormone from pituitary cells, decreased mitogenic response of lymphocytes, increased Interferon-alpha by lymphocytes, increased Interleukin-1 and Tumor Necrosis Factor secretion by macrophages. Related experiments on cells immediately postflight and on procaryotic cells have shown significant changes in secretory capacity, cell proliferation, differentiation and development. Postulated mechanism include altered cell-cell interactions, altered calcium ion transport, effects on cell cytoskeleton, transport of transmitters and interactions with receptors. The discussion includes use of new molecular methods, considerations for cell environmental control and a preview of several experiments planned for the Shuttle and Spacelab flights to study the basic effects of microgravity on cellular physiology and potential interactions of spaceflight with radiation damage and cellular repair mechanisms.

Animals↗

PubMed1986

Lipoxygenase metabolites of arachidonic acid and the development of ischaemic cerebral oedema.

This study examined the changes in cerebral blood flow, water content, and lipoxygenase metabolites (leukotrienes) following bilateral carotid artery occlusion (BCO) and reperfusion in the gerbil. The effect of inhibiting lipoxygenase with nordihydroguaretic acid (NDGA) was also examined. BCO caused cerebral blood flow (measured using H2 clearance) to decline from 23.5 +/- 1.9 to 4.5 +/- 1.9 ml/min/100 gm. Reperfusion increased flow to 27.9 +/- 4 ml/min/100 gm at 10 min, which declined to 13.7 +/- 1.3 ml/min/100 gm at 50 min. Concomitant oedema measurement revealed brain specific gravity decreasing to 1.0402 +/- 0.0014 at 10 min and to 1.0325 +/- 0.0006 at 50 min reperfusion (nonoccluded controls). Leukotriene B4 (LTB4) increased from 26.8 +/- 4.6 to 33.5 +/- 2.1 pg/mg protein 10 min after reperfusion (p less than 0.05), but declined to 21.8 +/- pg/mg protein by 100 min (vs nonischaemic control = 21.3 +/- 2.9 pg/mg protein). Activation of arachidonate metabolism was confirmed by significantly increased 6 keto PGF1 alpha. Pretreatment of the animals with NDGA did not alter CBF, but increased specific gravity above saline-treated controls at 50 min of reperfusion (NDGA = 1.0370 +/- 0.002 vs control = 1.0325 +/- 0.0006, p less than 0.05). Similarly, NDGA blunted the increase in LTB4 formation 10 min after reperfusion (control = 26.8 +/- 4.6 pg/mg protein vs NDGA = 29.7 +/- 2.9 pg/mg protein, p = N.S.). These findings indicate that LTB4 production is stimulated by BCO and reperfusion in the gerbil, and that this stimulation occurs early on in the reperfusion. Further, we observe that the lipoxygenase inhibitor NDGA limits the formation of ischaemic cerebral oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Microgravity effects on the oogenesis and development of embryos of Drosophila melanogaster laid in the Spaceshuttle during the Biorack experiment (ESA).

The results obtained during the last successful flight of the Challenger Shuttle, in early November 1985, indicate that oogenesis and embryonic development of Drosophila melanogaster are altered in the absence of gravity. Two hundred forty females and ninety males, wild type Oregon R Drosophila melanogaster flies were flown in the Spaceshuttle during the 7-day D-1 mission and the embryos laid during the spaceflight were recovered and studied. Although some eggs developed into normal 1st instar larvae and many into late embryos in the 23 +/- 2 h collection periods throughout the flight, several interesting differences from the parallel ground and in-flight centrifuge controls were observed: 1) There was an increase in oocyte production and size. 2) There was a significant decrease in the number of larvae hatched from the embryonic cuticles in microgravity. 3) The majority of embryos were normally fertilized and at late stages of development, except in the space-flown containers in microgravity where a percentage of earlier stage embryos were recovered showing alterations in the deposition of yolk. 4) In correspondence with these results, at least 25% of the living embryos recovered from space failed to develop into adults. 5) Studies of the larval cuticles and those of the late embryos indicate the existence of alterations in the anterior, head and thoracic regions of the animals. 6) There was a delay in the development into adults of the embryos and larvae that had been subjected to microgravity and recovered from the space shuttle at the end of the flight. No significant accumulation of lethal mutations in any of the experimental conditions was detected as measured through the male to female ratio in the descendant generation. It seems that Drosophila melanogaster flies are able to sense and respond to the absence of gravity, changing several developmental processes even in very short space flights. The results suggest an interference with the distribution and/or deposition of the maternal components involved in the specification of the anterioposterior axis of the embryo.

Animals↗