Sphingolipids in human lens membranes: an update on their composition and possible biological implications

The unique nature of the most abundant phospholipids in human lens membranes remained overlooked until the 1990s when it was possible to discern dihydrosphingomyelins (DHSMs) from the more common sphingomyelins (SMs). Unlike in other mammalian membranes, DHSMs comprise nearly half of the phospholipids in adult human lenses. Compared to SMs with a trans double bond between carbons 4 and 5 of the sphingoid backbone, the absence of this unsaturation site in DHSMs allows the participation of the OH group on C3 in intermolecular H-bonds and leads to stronger interlipid interactions with both neighboring DHSMs and cholesterol. Phospholipid compositional changes with age and lens region observed in mammals with various life spans and lens growth rates, suggest that the highest levels of DHSMs along with the lowest amounts of phosphatidylcholines and SMs are found in lenses with the lowest growth rate, namely human lenses. The participation of phospholipid metabolites in the control of mitosis and elongation of lens cells is plausible and deserves investigation.     

Acute effects of 50 Hz magnetic field exposure on human visual task and cardiovascular performance

One hundred subjects, males and females with ages ranging between 18 and 48 years, were studied under both field-exposed and sham-exposed conditions. A 50 Hz, 100 μT magnetic field (MF) was used. To examine the effect of field exposure on performance, a two-alternative, forced-choice, duration-discrimination task with three levels of difficulty was used. The subject's task was to decide which of two sequentially presented light flashes had the longer duration. The standard duration was 50 ms, and the alternative durations were 65, 100, or 125 ms. Both reaction time and percentage of correct responses were recorded for each subject. MF and sham exposure were for 9 min each. Blood pressure and heart rate were also measured before and following MF exposure and sham-exposure trials. The study was performed double blind, with the exposure order counterbalanced. Compared to sham exposure, MF exposure significantly decreased reaction time on the hardest level of the performance task. MF exposure did not reliably affect percentage correct or cardiovascular performance. It was demonstrated that a relatively high level of statistical power was the basis for the observed MF effect, and the need to pay closer attention to power levels in future research is discussed. © 1996 Wiley-Liss, Inc.     

Alteration in the ubiquitin structure and function in the human lens: a possible mechanism of senile cataractogenesis

High-performance liquid chromatography purification followed by mass spectrometry analyses highlighted that human senile cataractous lens includes a 8182 Da species which is absent in the normal lens, whereas a 8566/8583 Da species is present in both lenses. Western blot analysis identified both species as ubiquitin. The species at lower molecular weight is a shorter form due to the cleavage of the C-terminal residues 73-76. As it is the last amino acid of ubiquitin which is involved in the protein degradation mechanism, we suggest that this structure modification compromises the function of ubiquitin and consequently the physiologically occurring degradation of the lens proteins.     

Venom,speed, and caution: effects on performance in a visual search task

Previous reports of faster responses to threatening compared to benign stimuli in visual search tasks have argued that threatening targets are faster to engage and slower to disengage attention than benign targets. This study reinterprets previous findings and resolves inconsistencies in the literature by replacing the theory of differential disengagement of attention with one of differential caution. It also examines whether visual attentional mechanisms are sensitive to more than just the threatening versus benign categorical status of the targets and introduces a novel measure (a caution score) that appears to be sensitive to the level of threat implied by the target image, but immune to other stimulus features (target-distracter similarity and threat status of distracters) known to affect reaction time. As well as locating threatening targets faster than benign targets, participants were also faster, more accurate, and more cautious to detect lethal spiders compared to nonlethal spiders and even more cautious again if the spiders were presented on a person's hand. These results suggest that mechanisms of attention and threat evaluation interact during visual search tasks, producing behaviour that is sensitive to the target's implied threat level and the context in which that target is presented.     

Total-body irradiation with high-LET particles: acute and chronic effects on the immune system

Although the immune system is highly susceptible to radiation-induced damage, consequences of high linear energy transfer (LET) radiation remain unclear. This study evaluated the effects of 0.1 gray (Gy), 0.5 Gy, and 2.0 Gy iron ion (56Fe(26)) radiation on lymphoid cells and organs of C57BL/6 mice on days 4 and 113 after whole body exposure; a group irradiated with 2.0 Gy silicon ions (28Si) was euthanized on day 113. On day 4 after 56Fe irradiation, dose-dependent decreases were noted in spleen and thymus masses and all major leukocyte populations in blood and spleen. The CD19(+) B lymphocytes were most radiosensitive and NK1.1(+) natural killer (NK) cells were most resistant. CD3(+) T cells were moderately radiosensitive and a greater loss of CD3(+)/CD8(+) T(C) cells than CD3(+)/CD4(+) T(H) cells was noted. Basal DNA synthesis was elevated on day 4, but response to mitogens and secretion of interleukin-2 and tumor necrosis factor-alpha were unaffected. Signs of anemia were noted. By day 113, high B cell numbers and low T(C) cell and monocyte percents were found in the 2.0 Gy 56Fe group; the 2.0 Gy 2)Si mice had low NK cells, decreased basal DNA synthesis, and a somewhat increased response to two mitogens. Collectively, the data show that lymphoid cells and tissues are markedly affected by high linear energy transfer (LET) radiation at relatively low doses, that some aberrations persist long after exposure, and that different consequences may be induced by various densely ionizing particles. Thus simultaneous exposure to multiple radiation sources could lead to a broader spectrum of immune dysfunction than currently anticipated.     

Melanopsin regulates visual processing in the mouse retina

The discovery of melanopsin-dependent inner retinal photoreceptors in mammals has precipitated a fundamental reassessment of such non-image forming (NIF) light responses as circadian photoentrainment and the pupil light reflex. By contrast, it remains unclear whether these new photoreceptors also play a role in classical image-forming vision. The retinal ganglion cells that subserve inner retinal photoreception (ipRGCs) project overwhelmingly to brain areas involved in NIF responses, indicating that, in terms of central signaling, their predominant function is non-image forming. However, ipRGCs also exhibit intraretinal communication via gap junction coupling, which could allow them to modulate classical visual pathways within this tissue. Here, we explore this second possibility by using melanopsin knockout (Opn4-/-) mice to examine the role of inner retinal photoreceptors in diurnal regulation of retinal function. By using electroretinography in wild-type mice, we describe diurnal rhythms in both the amplitude and speed of the retinal cone pathway that are a function of both prior light exposure and circadian phase. Unexpectedly, loss of the melanopsin gene abolishes circadian control of these parameters, causing significant attenuation of the diurnal variation in cone vision. Our results demonstrate for the first time a melanopsin-dependent regulation of visual processing within the retina, revealing an important function for inner retinal photoreceptors in optimizing classical visual pathways according to time of day.     

Melanopsin mediates retrograde visual signaling in the retina

The canonical flow of visual signals proceeds from outer to inner retina (photoreceptors→bipolar cells→ganglion cells). However, melanopsin-expressing ganglion cells are photosensitive and functional sustained light signaling to retinal dopaminergic interneurons persists in the absence of rods and cones. Here we show that the sustained-type light response of retinal dopamine neurons requires melanopsin and that the response is mediated by AMPA-type glutamate receptors, defining a retrograde retinal visual signaling pathway that fully reverses the usual flow of light signals in retinal circuits.     

Regulation and possible role of serotonin N-acetyltransferase in the retina

The activity of retinal serotonin N-acetyltransferase (NAT) (arylamine acetyltransferase, EC 2.3.1.5), the penultimate enzyme in melatonin biosynthesis, exhibits properties of a circadian rhythm comparable to that seen in the pineal gland. Using an eye cup preparation we have found that circadian properties persist in vitro, which indicates that an endogenous circadian oscillator controlling NAT is present in the eye. Nighttime increases in NAT activity are suppressed by light, protein synthesis inhibitors, and catecholamines. In light, NAT activity is induced by conditions expected to increase intracellular levels of cyclic AMP (cAMP). This suggests that catecholamines and cAMP are normally involved in the regulation of NAT. Circadian indoleamine metabolism may play a role in the control of rhythmic photoreceptor metabolism as evidenced by the observation that melatonin and related compounds are potent activators of disk shedding.     

Ca(2+)-binding proteins in the retina: structure, function, and the etiology of human visual diseases

The complex sensation of vision begins with the relatively simple photoisomerization of the visual pigment chromophore 11-cis-retinal to its all-trans configuration. This event initiates a series of biochemical reactions that are collectively referred to as phototransduction, which ultimately lead to a change in the electrochemical signaling of the photoreceptor cell. To operate in a wide range of light intensities, however, the phototransduction pathway must allow for adjustments to background light. These take place through physiological adaptation processes that rely primarily on Ca(2+) ions. While Ca(2+) may modulate some activities directly, it is more often the case that Ca(2+)-binding proteins mediate between transient changes in the concentration of Ca(2+) and the adaptation processes that are associated with phototransduction. Recently, combined genetic, physiological, and biochemical analyses have yielded new insights about the properties and functions of many phototransduction-specific components, including some novel Ca(2+)-binding proteins. Understanding these Ca(2+)-binding proteins will provide a more complete picture of visual transduction, including the mechanisms associated with adaptation, and of related degenerative diseases.     

ACTH 4-9 effects on the human visual event-related potential

Three oral doses (5, 10 and 20 mg) of an analog of ACTH 4-9 were compared with a vehicle control and d-amphetamine (10 mg). In a double-blind procedure, five men and five women were tested at weekly intervals with each treatment. In each session, four visual event-related potentials (ERPs) were recorded at hourly intervals. Visual ERPs were averaged from the electroencephalogram recorded from the left and right hemisphere. Dosage, time after administration, hemisphere of the brain and sex of the subject influenced the ERP. The ACTH 4-9 analog decreased amplitude of P100 but increased integrated activity of the ERP. This effect peaked at 60 minutes then "recovered." The effects of the peptide were more pronounced with doses of 5 and 10 mg, in the right hemisphere of men and in the left hemisphere of women. The findings indicated that the ACTH 4-9 analog influenced components of ERP commonly related to the perceptual/attentional state of the organism in a sexually dimorphic manner.     

Delayed matching to sample: the effects of sample-set size on human performance

The discriminative performance of students was assessed on a delayed-matching-to-sample task (DMST) using disks, presented by a computer, as stimuli. The size of the non-matching comparison stimuli was changed, for each participant, until each was 100% correct at 0.05 s delay. Then delays of 0.05, 2, 4, 8 and 16 s were paired with each of one, four, eight, 16, and 32 sample stimuli. Accuracy generally decreased over the one, four and eight samples, did not change consistently over the largest sample-set sizes and decreased as delay increased. Both delay and sample-set size had statistically significant main effects, their interaction was not significant. Fitted exponential functions gave a measure of discrimination at zero delay, a, and a measure of the rate of decrement in performance with increasing delay, b. As number of sample stimuli increased there was no systematic change in b, while a decreased most over one to four samples, decreased less with eight samples, and decreased least from 16 to 32 samples. These results suggest that the effects of varying sample-set size depends on the range of sizes studied, thus, they provide a possible explanation for some previous disparate findings. They also suggest that it might be proactive interference that leads to decreases in accuracy with increasing sample-set size.     

Chest wall mechanics: effects of acute and chronic lung disease

Data from the literature show that lung tissue properties affect the chest wall compliance, Ccw, which is the change in lung volume, Vl, with respect to the pleural pressure, Ppl. to analyze the difference between acute and chronic lung tissue changes, we used a mathematical model that describes the static, nonlinear mechanics of the ventilatory system in terms of its major elements: rib cage; abdomen; diaphragm and lung. With this model we derived the relationship between chest wall, rib-cage and diaphragm compliances. Although the Vl-Ppl relation is independent of lung mechanics, the volume operating point (FRC) of the ventilatory system depends on lung tissue properties. This accounts for the effect of acute lung abnormalities. In the presence of chronic lung abnormalities, the properties of the rib-cage are changed which shifts the entire Vl-Ppl curve. In general, valid comparisons of (extra-pulmonary) chest wall mechanics can only be made using the entire Vl-Ppl relation, or at least a sufficiently large part of the relation about FRC. Differentiation of the rib-cage and diaphragm mechanics requires additional measurements of the rib-cage A-P distance and the relative position of the diaphragm.