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Psychosocial adaptation of 39 adolescents with sex chromosome abnormalities.

OBJECTIVES: Children with sex chromosome abnormalities (SCA) are known to be at increased risk for neuromotor, language, learning, and behavioral problems, but little is known of psychosocial adaptation of SCA adolescents. This study was conducted to evaluate psychologic characteristics of unselected SCA adolescents, including socialization, educational progress, separation from family, and incidence and severity of psychiatric disturbance. METHODS: Thirty-nine propositi identified through the screening of 40,000 consecutive Denver newborns, including boys with 47,XXY karyotypes and girls with 47,XXX, 45,X, and partial X monosomy, or SCA mosaic karyotypes, have been followed longitudinally into adolescence. Twenty-seven siblings served as controls. Between 12 and 19 years of age, all participated in blind psychiatric interviews and were administered standardized intelligence and achievement tests. RESULTS: SCA propositi demonstrated a mean IQ score 21 points lower than that of control subjects. In addition, lower mean scores were seen on achievement test results as well as lower overall psychosocial adaptation scores and increased incidence of psychiatric disturbance. Depression was the most frequent psychiatric diagnosis. Propositi were more likely to receive special education assistance in high school and were less likely to graduate from high school than were controls. Of the three nonmosaic propositi groups, the 47,XXX girls demonstrated the poorest overall psychosocial adaptation and highest degree of psychiatric disturbance. Mosaic girls were indistinguishable from control subjects. Marked variability was found among all three nonmosaic groups, with some individuals in each group demonstrating relatively strong psychosocial adaptation. CONCLUSIONS: The presence of nonmosaic sex chromosome abnormality increases the risk for impeded cognitive skills, learning abilities, and psychosocial adaptation in adolescence. The factors that allow for stronger adaptation in some of these adolescents include the presence of a stable and supportive family environment. The outlook for adaptation in unselected SCA adults remains uncertain.

Achievement↗

Induction of radio-adaptive response by low-dose X-irradiation on chromosome aberrations in human embryonic fibroblasts.

Inonizing radiation induces mutation and chromosome aberrations in the irradiated cells. However, the frequency of chromosome aberrations induced by high-dose X-ray irradiation is diminished in cells exposed to low-dose pre-irradiation. The radio-adaptive response induced by low-dose radiation has been previously reported. These studies usually choose V79 cells or human peripheral lymphocytes as test materials. However, V79 cells are no longer normal diploid cells and in the case of human peripheral lymphocytes, artificial blastoid transformation by a mitogen is necessary for the experiments. In order to observe the radio-adaptive response of normal cells under natural conditions, we elected to study human embryonic fibroblasts as cells in the normal cell cycle under natural conditions. We investigated the dose dependency of the frequency of chromosome aberrations induced by radiation, conditions required to induce the radio-adaptive response, and the relationship between radio-adaptive response and protein production system. As a result, the number of chromosome aberrations significantly increased with high dose irradiation as a function of dose. When a conditioning irradiation of 10 cGy was given to cells 4 hours before the irradiation of 150 cGy, the number of chromosome aberrations significantly decreased. However, the induction of this radio-adaptive response was inhibited by treatment with 1 microgram/ml of cycloheximide during the 2 to 4 hour period after conditioning irradiation. These findings possibly suggest that the radio-adaptive response can be induced by pre-irradiation with about 10 cGy and that X-ray induced protein influences the induction of radio-adaptive response.

Acclimatization↗

Enhancement of mitogen-stimulated proliferation of low dose radiation-adapted mouse splenocytes.

We have monitored mitogen-stimulated mouse splenocyte proliferation as a biological end point of radiation damages to access adaptive response to ionizing radiation. When cells were pre-exposed to an adapting dose of 0. 01 Gy of low dose gamma-ray 4, 7, and 20 hours prior to an acute challenging dose of 2 Gy, most significant enhancement in splenocyte proliferation was induced at 4 hour interval. When the challenging high dose was varied, an adaptive response was observed at up to 4 Gy of high dose gamma-ray challenge. Gamma-ray-irradiated mouse splenocyte showed characteristic morphology of apoptotic cells. The extent of DNA fragmentation, another characteristic of apoptotic cells, was also reduced in low dose gamma-ray-adapted cells. The addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazol (DRFB), respectively during adaptation period, the period between low and high dose irradiations, were able to inhibit the induction of adaptive response. These data suggest that to induce adaptive response to ionizing radiation in mouse splenocytes, both protein and RNA synthesis are required.

Animals↗

The endogenous calcium buffer and the time course of transducer adaptation in auditory hair cells.

Mechanoelectrical transducer currents in turtle auditory hair cells adapt to maintained stimuli via a Ca2+-dependent mechanism that is sensitive to the level of internal calcium buffer. We have used the properties of transducer adaptation to compare the effects of exogenous calcium buffers in the patch electrode solution with those of the endogenous buffer assayed with perforated-patch recording. The endogenous buffer of the hair bundle was equivalent to 0.1-0.4 mM BAPTA and, in a majority of cells, supported adaptation in an external Ca2+ concentration of 70 microM similar to that in turtle endolymph. The endogenous buffer had a higher effective concentration, and the adaptation time constant was faster in cells at the high-frequency end than at the low-frequency end of the cochlea. Experiments using buffers with different Ca2+-binding rates or dissociation constants indicated that the speed of adaptation and the resting open probability of the transducer channels could be differentially regulated and imply that the endogenous buffer must be a fast, high-affinity buffer. In some hair cells, the transducer current did not decay exponentially during a sustained stimulus but displayed damped oscillations at a frequency (58-230 Hz) that depended on external Ca2+ concentration. The gradient in adaptation time constant and the tuned transducer current at physiological levels of calcium buffer and external Ca2+ suggest that transducer adaptation may contribute to hair cell frequency selectivity. The results are discussed in terms of feedback regulation of transducer channels mediated by Ca2+ binding at two intracellular sites.

Animals↗

Visual-motor adaptation. Quantitative demonstration in patients with posterior fossa involvement.

Short-term visual-motor adaptation to magnifying spectacle lenses was studied in normal subjects and in patients with nonacute posterior fossa lesions. When normal subjects, looking through magnifying lenses, pointed open loop to targets without viewing their hands, they initially underestimated the distance (magnification effect). After a 20-minute close-loop training or adaptation exposure period during which they viewed the performance of their hands, a modified visual-motor scheme evolved, compensating for about half of the lens-induced pointing error (adaptation effect). Removal of the lenses after adaptation caused open-loop, overshooting pointing errors (adaptation after-effect). Four patients with remission of cerebellar signs showed normal visual-motor adaptive performance, evidence of ability to recalibrate gain. One patient with persisting cerebellar ataxia was unable to recalibrate gain during close-loop visual-motor training. His history of transient palatal myoclonus implicates a role for the cerebellar-olivary system in calibration of visual-motor gain.

Adaptation, Ocular↗

Fine structure of the retinal pigment epithelium of Oreochromis niloticus L. (Cichlidae; Teleostei) in light- and-dark adaptation.

The fine structure of the retinal pigment epithelium (RPE) of the cichlid Oreochromis niloticus was investigated in both light- and dark-adaptation. The eyes of four light-adapted and from four dark-adapted O. niloticus were fixed routinely for light and transmission electron microscopy. The RPE consisted of a single layer of columnar cells showing minimal basal infolding but plentiful apical processes that in light-adaptation interdigitated with the photoreceptor outer segments. The epithelial cells were joined by a series of basally-located tight junctions. These cells showed a large vesicular nucleus, plentiful smooth endoplasmic reticulum and polysomes, but only small amounts of rough endoplasmic reticulum. Phagosomes, lysosome-like bodies, lipid droplets, and myeloid bodies were observed. The choriocapillaris was a single layer of large-caliber capillaries, and Bruch's membrane (complexus basalis) was a trilaminate structure typical of teleosts. The RPE melanosomes moved basally (sclerally) in dark-adaptation and apically (vitreally) during light-adaptation. Other morphological features which changed at least to some degree during retinomotor responses were: the location of the RPE nucleus; the location and electron density of the mitochondria; and the location, number, and size of the myeloid bodies. A number of unique morphological changes take place within the RPE cells of this species during the circadian cycle in addition to the movement of melanosomes characterized in other vertebrates.

Adaptation, Ocular↗

Two concepts of adaptation: Darwin's and psychology's.

The paper takes issue with the traditional view of Darwin's influence on psychology; namely, that it is he who passed on to psychology the concept of individual adaptation. Three arguments are presented: a) that Darwin, qua scientist, was only interested in species adaptation, an entirely different concept from that of individual adaptation, b) that Darwin's writings on individual adaptation are so unexceptional that it is inconceivable that psychologists should have been influenced by them and c) that the two concepts are logically incompatible since species adaptation presupposes a strict hereditary determinism, while individual adaptation conceives of the organism either as free and undetermined or else as determined by the environment.

Adaptation, Biological↗

Alteration of metabolism of retinal taurine following prolonged light and dark adaptation: a quantitative comparison with gamma-aminobutyric acid (GABA).

Alteration of metabolism of taurine in prolonged light- and dark-adapted frog retinae were studied in comparison with that of gamma-aminobutyric acid (GABA) and the following results were obtained. (1) Statistically significant alterations in retinal taurine, an increase in dark-adapted, and a decrease in light-adapted states, respectively, occurred when frogs were adapted continuously to light or dark for more than 3 weeks. Under the same experimental conditions, no alteration in retinal GABA was noted. (2) At 3 weeks and thereafter, a significant increase of retinal cysteine sulfinic acid decarboxylase (CSD; EC 4.1.1.12) activity, an enzyme involved in the biosynthetic pathway of taurine, also occurred in the dark, whereas the activity in the light-adapted retina was reduced. On the other hand, the retinal activity of L-glutamate decarboxylase (GAD; EC 1.1.1.15), the rate-limiting enzyme of GABA biosynthesis, was not altered in dark- as well as light-adapted state. Similarly, retinal GABA-transaminase (GABA-T; EC 2.6.1.19)-succinic semialdehyde dehydrogenase (SSADH; EC 1.2.1.16) was unaltered. (3) These alterations in retinal taurine were, however, unaccompanied by any changes in factors related to transmitter actions such as evoked release, high affinity uptake, and specific binding to synaptic membranes. The above results suggest that, different from GABA as a potent candidate for inhibitory neurotransmitter, retinal taurine may act as neuromodulator and/or may play an important role as a basic factor for maintaining cellular integrity under certain pathophysiological conditions.

4-Aminobutyrate Transaminase↗

An analysis of rod outer segment adaptation based on a simple equivalent circuit.

This model of rod outer segment adaptation is based on the hypothesis that transmitter substance released by bleached rhodopsin closes sodium channels in the outer segment plasma membrane, leading to hyperpolarization of the receptor. The outer segment adaptation processes of the model are associated with the transmitter release, the transmitter background concentration and the plasma membrane leakage. Changes in the three model parameters correspond to the three types of outer segment adaptation process. According to the model the stimulus-response function is in every adaptational state U/Umax = I/(I + IH). The model predicts how each adaptation process affects IH and Umax. Specifically, when the number of liberated transmitter molecules per isomerizing quantum decreases, the amplitude Umax remains constant but IH increases. A short description of this model has been published in a paper reporting experimental results on background adaptation (Hemilä, 1977).

Adaptation, Ocular↗

Nitric oxide controls the light adaptive chromatic difference in receptive field size of H1 horizontal cell network in carp retina.

In carp retina, the receptive field size of the H1-type horizontal cell (HC) network is known to be chromatically selective, as electrophysiological signals are generated by short-wavelength (SW) light stimuli, which spread much less than those for long-wavelength (LW). We have shown previously that the signalling mechanism underlying this chromatic difference operates only in the light-adapted retina and that it involves cGMP as an intermediary messenger. In the present study, the possible role of nitric oxide (NO) as such a control mechanism was investigated. Application of a NO donor (SNP or SNOG) to dark-adapted retinae produced a chromatic difference in the receptive field size, such as in the light-adapted state. This effect was due mainly to a reduction in the spread of signals generated by SW stimuli; LW signalling spread was not altered. No such effect was observed in light-adapted retinae where a chromatic difference in receptive field size was already present. On the other hand, application of the NO 'scavenger' haemoglobin to light-adapted retinae suppressed the chromatic difference. These results are consistent with NO being a light-adaptive retinal neuromodulator involved in the generation of the chromatic difference in H1 cell receptive field size. These results are discussed in the context of two different hypotheses.

Action Potentials↗

Multi-omics reveal molecular changes during suspension adaptation of HEK293 cells.

Human embryonic kidney 293 (HEK293) cells have been successfully adapted from adherent to suspension culture and widely applied in both scientific research and the pharmaceutical industry. Although some studies investigated the variances between established adherent and suspension HEK293 cells of different strains, specific alterations in the cells during this consecutive process of suspension adaptation and possible factors driving this process have not been well described. Here, we adapted adherent HEK293 to suspension with desirable cell growth and high productivity for recombinant adenoviral vectors, and cells at several stages throughout the process were characterized. Slower cell growth, lower glucose uptake, increased lactate production, and weaker cell-surface adhesion were observed in suspension cells compared to their adherent counterparts. We further performed transcriptomics, proteomics, and metabolomics analysis to identify key cellular switches. A total of 2476 differentially expressed genes were found, including 1218 upregulated and 1258 downregulated genes in suspension cells. A similar and correlated pattern was observed in the proteomic study, and 702 differentially expressed metabolites were identified by untargeted metabolomics. In light of enrichment analysis, we summarized that HEK293 adherent cells survived and adapted to suspension culture via structural remodeling, metabolic shift and stress resistance. Our results provide a molecular enlightenment for suspension adaptation and potential directions for rational modification of HEK293 cell lines for future use. KEY POINTS: • Suspension adaptation reduced adhesion and reshaped the HEK293 cytoskeleton. • Multi-omics revealed metabolic rewiring and enhanced stress resistance. • An optimized suspension line outperformed an internal HEK293 suspension reference.

Humans↗

Distribution of phosphorylated protein kinase C alpha in goldfish retinal bipolar synaptic terminals: control by state of adaptation and pharmacological treatment.

Protein kinase C (PKC) is a signalling enzyme critically involved in many aspects of synaptic plasticity. In cyprinid retinae, the PKC alpha isoform is localized in a subpopulation of depolarizing bipolar cells that show adaptation-related morphological changes of their axon terminals. We have studied the subcellular localization of phosphorylated PKC alpha (pPKC alpha) in retinae under various conditions by immunohistochemistry with a phosphospecific antibody. In dark-adapted retinae, pPKC alpha immunoreactivity is weak in the cytoplasm of synaptic terminals, labelling being predominantly associated with the membrane compartment. In light-adapted cells, immunoreactivity is diffusely distributed throughout the terminal. Western blot analysis has revealed a reduction of pPKC alpha immunoreactivity in cytosolic fractions of homogenized dark-adapted retinae compared with light-adapted retinae. Pharmacological experiments with the isoform-specific PKC blocker Goe6976 have shown that inhibition of the enzyme influences immunolabelling for pPKC alpha, mimicking the effects of light on the subcellular distribution of immunoreactivity. Our findings suggest that the state of adaptation modifies the subcellular localization of a signalling molecule (PKC alpha) at the ribbon-type synaptic complex. We propose that changes in the subcellular distribution of PKC alpha immunoreactivity might be one component regulating the strength of the signal transfer of the bipolar cell terminal.

Adaptation, Ocular↗

Application of visually evoked response near the threshold of vision to objective measurement of dark adaptation.

The visually evoked response (VER) to dim lights with intensities within the scotopic or lower mesopic range increased in amplitude during the progressive dark adaptation. The VER amplitude vs. time curve resembled the psychophysical dark adaptation curve. The spectral sensitivity curve of the dark-adapted VER matched the C.I.E. scotopic sensitivity curve. The dark-adapted VER was abnormal in patients with retinitis pigmentosa and with congenital stationary night blindness and recordable in a patient with cone dysfunction. There was a close correlation between the VER threshold and subjective threshold of visual perception. The dark-adapted VER may be useful as an objective index of dark adaptation.

Adaptation, Ocular↗

Photoreceptor adaptation in intrinsically photosensitive retinal ganglion cells.

A rare type of mammalian retinal ganglion cell (RGC) expresses the photopigment melanopsin and is a photoreceptor. These intrinsically photosensitive RGCs (ipRGCs) drive circadian-clock resetting, pupillary constriction, and other non-image-forming photic responses. Both the light responses of ipRGCs and the behaviors they drive are remarkably sustained, raising the possibility that, unlike rods and cones, ipRGCs do not adjust their sensitivity according to lighting conditions ("adaptation"). We found, to the contrary, that ipRGC sensitivity is plastic, strongly influenced by lighting history. When exposed to a constant, bright background, the background-evoked response decayed, and responses to superimposed flashes grew in amplitude, indicating light adaptation. After extinction of a light-adapting background, sensitivity recovered progressively in darkness, indicating dark adaptation. Because these adjustments in sensitivity persisted when synapses were blocked, they constitute "photoreceptor adaptation" rather than "network adaptation." Implications for the mechanisms generating various non-image-forming visual responses are discussed.

Action Potentials↗

Absolute and spectral sensitivities in dark- and light-adapted Pagothenia borchgrevinki, an Antarctic nototheniid fish.

Functional properties of the retina of Pagothenia borchgrevinki, an Antarctic nototheniid fish that lives beneath the 2.5-3 m thick sea-ice in water of -1.8 degrees C temperature, were analyzed electrophysiologically at Scott Base (77 degrees 50'S; 166 degrees 45'E). The waveform of the ERG was monophasic in the dark-adapted state and showed an off-response of opposite polarity in the light-adapted condition. Responses of the light-adapted retina were smaller than those of the dark-adapted eye, although both photopic and scotopic components were observed. Spectral sensitivity measured by monochromatic photostimulation at 14 different wavelengths across the 400-700-nm range showed a single maximum at 490 nm. The spectral sensitivity curve is consistent with a rhodopsin photopigment. The dark-adapted retina exhibited a photon flux density threshold of approximately 2 x 10(9) photons cm-2 s-1) when monochromatic flashes of 500 nm wavelength and 250 ms duration were used. When the stimulus consisted of 1 s white light, a minimum energy flux density of approx. 2 x 10(-4) microW/cm2 was necessary to elicit a detectable response. It was concluded that the visual system of P. borchgrevinki was in tune with the dominant downwelling spectral irradiance and that, due to retinal thermal noise reduction in the cold environment, no great need for particular anatomical adaptations to further enhance sensitivity existed.

Acclimatization↗

Adaptation and the color statistics of natural images.

Color perception depends profoundly on adaptation processes that adjust sensitivity in response to the prevailing pattern of stimulation. We examined how color sensitivity and appearance might be influenced by adaptation to the color distributions characteristic of natural images. Color distributions were measured for natural scenes by sampling an array of locations within each scene with a spectroradiometer, or by recording each scene with a digital camera successively through 31 interference filters. The images were used to reconstruct the L, M and S cone excitation at each spatial location, and the contrasts along three post-receptoral axes [L + M, L - M or S - (L + M)]. Individual scenes varied substantially in their mean chromaticity and luminance, in the principal color-luminance axes of their distributions, and in the range of contrasts in their distributions. Chromatic contrasts were biased along a relatively narrow range of bluish to yellowish-green angles, lying roughly between the S - (L + M) axis (which was more characteristic of scenes with lush vegetation and little sky) and a unique blue-yellow axis (which was more typical of arid scenes). For many scenes L - M and S - (L + M) signals were highly correlated, with weaker correlations between luminance and chromaticity. We use a two-stage model (von Kries scaling followed by decorrelation) to show how the appearance of colors may be altered by light adaptation to the mean of the distributions and by contrast adaptation to the contrast range and principal axes of the distributions; and we show that such adjustments are qualitatively consistent with empirical measurements of asymmetric color matches obtained after adaptation to successive random samples drawn from natural distributions of chromaticities and lightnesses. Such adaptation effects define the natural range of operating states of the visual system.

Adaptation, Ocular↗

NADPH diaphorase activity in mammalian retinas is modulated by the state of visual adaptation.

NADPH diaphorase histochemistry is commonly used to identify cells containing nitric oxide synthase (NOS), the enzyme catalyzing the production of nitric oxide from L-arginine. NADPH diaphorase activity and NOS immunostaining was demonstrated in different cells of the vertebrate retina; photoreceptors, horizontal cells, amacrine cells, ganglion cells, and Müller cells. However, the physiological role of nitric oxide (NO) in the retina has yet to be elucidated. In this study, we tested the assumption that NADPH diaphorase activity in the retinas of rabbits and rats depended on the state of visual adaptation. In the rabbit, light adaptation enhanced NADPH diaphorase activity in amacrine cells and practically eliminated it in horizontal cells. Dark adaptation induced the opposite effects; the NADPH diaphorase activity was reduced in amacrine cells and enhanced in horizontal cells. Retinas from eyes that were injected intravitreally with L-glutamate exhibited a pattern of NADPH diaphorase activity that was similar to that seen in dark-adapted retinas. In rats, the NADPH diaphorase activity of amacrine and horizontal cells exhibited adaptation dependency similar to that of the rabbit retina. But, the most pronounced effect of dark adaptation in the rat's retina was an enhancement of NADPH diaphorase activity in Müller cells, especially of the endfoot region. Assuming that NADPH diaphorase activity is a marker for NOS, these findings suggest that NO production in the mammalian retina is modulated by the level of ambient illumination and support the notion that NO plays a physiological role in the retina.

Adaptation, Ocular↗

Influence of rod adaptation upon cone responses to light offset in humans: II. Results in an observer with exaggerated suppressive rod-cone interaction.

In normal observers, sensitivity of cones to rapid sinusoidal flicker decreases by about 0.7 log units as rods progressively dark adapt. However, Arden and Hogg (1985) described a night-vision disorder characterized by normal rod sensitivity but exaggerated suppressive rod-cone interaction (SRCI). We refer to this condition as the exaggerated SRCI syndrome (ESS). The present paper examines the influence of rod-adaptation upon cone-mediated responses to light onset and offset in an observer with ESS. Under all conditions of adaptation examined, sensitivity of cones to rapid-on waveforms is indistinguishable to that of a normal observer tested under identical circumstances; rod sensitivity is also normal. However, the sensitivity of cones to transient decreases in illumination is clearly subnormal under light-adapted conditions. This deficit in cone responsiveness to light offset becomes increasingly subnormal as rods dark adapt and, when completely dark adapted, the ESS observer is nearly blind to 1 Hz rapid-off sawtooth waveforms. These results strongly bolster previous results that suggest that suppressive rod-cone interaction is restricted to the response to transient decreases in illumination.

Adaptation, Ocular↗