Pronounced Individual Variations Research Articles

Changes in structural and pigmentary colours in response to cold stress in Polyommatus icarus butterflies

While numerous papers have investigated the effects of thermal stress on the pigmentary colours of butterfly wings, such studies regarding structural colours are mostly lacking, despite the important role they play in sexual communication. To gain insight into the possible differences between the responses of the two kinds of colouration, we investigated the effects of prolonged cold stress (cooling at 5 °C for up to 62 days) on the pupae of Polyommatus icarus butterflies. The wing surfaces coloured by photonic crystal-type nanoarchitectures (dorsal) and by pigments (ventral) showed markedly different behaviours. The ventral wing surfaces exhibited stress responses proportional in magnitude to the duration of cooling and showed the same trend for all individuals, irrespective of their sex. On the dorsal wing surface of the males, with blue structural colouration, a smaller magnitude response was found with much more pronounced individual variations, possibly revealing hidden genetic variations. Despite the typical, pigmented brown colour of the dorsal wing surface of the females, all cooled females exhibited a certain degree of blue colouration. UV-VIS spectroscopy, optical microscopy, and scanning and transmission electron microscopy were used to evaluate the magnitude and character of the changes induced by the prolonged cold stress.

Control of human energy expenditure by cytochrome c oxidase subunit IV-2.

Resting metabolic rate (RMR) in humans shows pronounced individual variations, but the underlying molecular mechanism remains elusive. Cytochrome c oxidase (COX) plays a key role in control of metabolic rate, and recent studies of the subunit 4 isoform 2 (COX IV-2) indicate involvement in the cellular response to hypoxia and oxidative stress. We evaluated whether the COX subunit IV isoform composition may explain the pronounced individual variations in resting metabolic rate (RMR). RMR was determined in healthy humans by indirect calorimetry and correlated to levels of COX IV-2 and COX IV-1 in vastus lateralis. Overexpression and knock down of the COX IV isoforms were performed in primary myotubes followed by evaluation of the cell respiration and production of reactive oxygen species. Here we show that COX IV-2 protein is constitutively expressed in human skeletal muscle and strongly correlated to RMR. Primary human myotubes overexpressing COX IV-2 displayed markedly (>60%) lower respiration, reduced (>50%) cellular H2O2 production, higher resistance toward both oxidative stress, and severe hypoxia compared with control cells. These results suggest an important role of isoform COX IV-2 in the control of energy expenditure, hypoxic tolerance, and mitochondrial ROS homeostasis in humans.

Biomarkers of cognitive dysfunction in traumatic brain injury

Acetylcholine, glutamate, dopamine, serotonin (5-HT), gamma-aminobutyric acid, substance P (SP), amyloid-β (Aβ) and neurotrophic protein S100B are arguably the most important cognition-related biomarkers in the brain. Among this list are five neurotransmitters that signal through postsynaptic receptors. Our knowledge of cognition-related biomarkers has been advanced through translational experiments and clinical case-study data. Although these biomarkers are widespread in the brain and pronounced individual variations exist, these biomarkers can be used to identify both acute and chronic abnormalities following traumatic brain injury. Changes in these biomarkers likely indicate damage to brain networks or to key brain cell types that support cognitive functions. Identification of such biomarker abnormalities could result in earlier diagnoses, improved prognoses and therapies that enable neurotransmitters to return to normal levels.

Inherited colour vision deficiencies: From Dalton to molecular genetics

In recent years, great advances have been made in our understanding of the molecular basis of colour vision defects, as well as of the patterns of genetic variation in individuals with normal colour vision. Molecular genetic analyses have explained the diversity of types and degrees of severity in colour vision anomalies, their frequencies, pronounced individual variations in test results, etc. New techniques have even enabled the determination of John Dalton's real colour vision defect, 150 years after his death. Inherited colour vision deficiencies most often result from the mutations of genes that encode cone opsins. Cone opsin genes are linked to chromosomes 7 (the S or "blue" gene) and X (the L or "red" gene and the M or "green" gene). The L and M genes are located on the q arm of the X chromosome in a head-to-tail array, composed of 2 to 6 (typically 3) genes--a single L is followed by one or more M genes. Only the first two genes of the array are expressed and contribute to the colour vision phenotype. The high degree of homology (96%) between the L and M genes predisposes them to unequal recombination, leading to gene deletion or the formation of hybrid genes (comprising portions of both the L and M genes), explaining the majority of the common red-green colour vision deficiencies. The severity of any deficiency is influenced by the difference in spectral sensitivity between the opsins encoded by the first two genes of the array. A rare defect, S monochromacy, is caused either by the deletion of the regulatory region of the array or by mutations that inactivate the L and M genes. Most recent research concerns the molecular basis of complete achromatopsia, a rare disorder that involves the complete loss of all cone function. This is not caused by mutations in opsin genes, but in other genes that encode cone-specific proteins, e.g. channel proteins and transducin.

Toward clinical application of prompt gamma spectroscopy for in vivo monitoring of boron uptake in boron neutron capture therapy.

In boron neutron capture therapy (BNCT) the absorbed dose to the tumor cells and healthy tissues depends critically on the boron uptake. Pronounced individual variations in the uptake patterns have been observed for two boron compounds currently used in clinical trials. This implies a high uncertainty in the determination of the boron dose component. In the present work a technique known as prompt gamma spectroscopy (PGS) is studied that potentially can be used for in vivo and noninvasive boron concentration determination at the time of the treatment. The technique is based upon measurement of gamma rays promptly emitted in the 10B(n,alpha)7Li and 1H(n,gamma)2D reactions. The aim of this work is to prepare the present setup for clinical application as a monitor of boron uptake in BNCT patients. Therefore, a full calibration and a set of phantom experiments were performed in a clinical setting. Specifically, a nonuniform boron distribution was studied; a skin/ dura, a larger blood vessel, and tumor within a head phantom was simulated. The results show that it is possible to determine a homogeneous boron concentration of 5 microg/g within +/-3% (1 standard deviation). In the nonuniform case, this work shows that the boron concentration can be determined through a multistep measurement procedure, however, with a somewhat higher uncertainty (approximately 10%). The present work forms the basis for a subsequent clinical application of the PGS setup aimed at in vivo monitoring of boron uptake.

Behavioural expression of laying hens in aviaries and cages: Frequencies, time budgets and facility utilisation

1. We studied: behavioural frequencies and time budgets of behaviour patterns in non-beak-trimmed White Leghorn layers housed in cages (720 cm2/hen, 3 hens/cage), and in the Marielund, the Tiered Wire Floor (TWF), and the Laco-Volétage aviaries (17 hens/m2 ground area); individual variation in behaviour among aviary hens; spatial utilisation of the different types of aviary. 2. At 25, 40, and 60 weeks of age behaviour patterns of 114 focal animals were data logged. Each bird was observed for 10 min 4 times a day on three consecutive days. 3. The frequency of activity transitions and the activity level was highest in TWF, second highest in cages, and lowest in Laco-Volétage, suggested that Laco-Volétage hens were the calmest, whereas birds in cages and in TWF were more restless. Abnormal types of behaviour occurred most often in cages and TWF. The disadvantageous behaviour patterns shown by birds in TWF and cages imply that these environments were the least appropriate for this layer strain. 4. Pronounced individual variations in mobility and facility utilisation were found, both within and between the three aviaries. Resting levels were used twice as much (Laco-Volétage), and litter areas one third as much (Marielund), as that expected on a simple a proportionate basis. Most feather pecking was performed at resting levels and on feeding floors, whereas most agonistic behaviour patterns were observed on feeding floors and litter. 5. Measures to improve the aviaries are outlined.

Ultrastructure of the aging human testis

The ultrastructure of the progressive testicular involution with advancing age in men is reviewed. There is no definite age at which testicular involution begins, and the onset and severity of testicular lesions are subjected to pronounced individual variations. Hormone studies also indicate great individual variations, and subtle changes in both the testis and the pituitary develop progressively with age. Testicular size, sperm quality, and numbers of all germ cell types, Sertoli cells, and Leydig cells decrease with age. The volume occupied by the seminiferous tubules decreases, whereas that occupied by the testicular interstitium remains constant. The most frequent histological pattern of the aging testis is a mosaic of different seminiferous tubule lesions, varying from tubules with complete, although reduced, spermatogenesis, to completely sclerosed tubules. The tubules with complete spermatogenesis may show numerous morphological abnormalities in the germ cells, including multinucleation. Abnormal germ cells degenerate causing Sertoli cell vacuolation. These vacuoles correspond to dilations of the extracellular spaces resulting from the premature exfoliation of germ cells. Degenerating cells that are phagocytosed by the Sertoli cells give rise to an accumulation of lipid droplets in the Sertoli cell cytoplasm. The loss of germ cells begins with the spermatids, but progressively affects the earlier germ cell types, and tubules with maturation arrest at the level of the spermatocytes or spermatogonia are observed. The Sertoli cells show morphological abnormalities such as dedifferentiation, mitochondrial metaplasia, and multinucleation. Germ cell loss is associated with thickening of the tunica propria. When all seminiferous epithelial cells have disappeared, only an intensely collagenized tunica propria with myoid cells remains (sclerosed tubules). The Leydig cells progressively dedifferentiate with a decrease in the quantity of both smooth endoplasmic reticulum and mitochondria, together with an accumulation of lipid droplets, crystalline inclusions, and residual bodies, and formation of multinucleate cells. The development of tubular involution with age is similar to that observed after experimental ischemia, suggesting that vascular lesions may play an important role in age-related testicular atrophy.

Structure of dental plaque and the plaque-enamel interface in human experimental caries.

This study describes the ultrastructure of dental plaque and the plaque-enamel interface after 2 and 3 weeks' exposure to a cariogenic challenge. Five dental students carried a total of 25 specimens of smooth surface enamel in intraoral acrylic appliances. During the initial 3 days the volunteers refrained from oral hygiene and performed nine daily mouthrinses with 10% (w/v) solutions of sucrose. After the 3rd day the volunteers cleaned their natural teeth, whereas the experimental sites were left undisturbed except for nine daily extraoral 5-min immersions in 5% (w/v) solutions of sucrose. Clinically, three patterns of colonization were observed after 3 days. At the histological level the experimental bacterial deposits also exhibited three distinctly different structural patterns after 2 and 3 weeks. Individual patterns consistently differed with regard to the microbial composition, the structural organization of the deposits, and the presence or absence of crystal-like material. However, in all individuals a layer of densely packed gram-positive bacteria resembling Actinomyces was consistently present close to the enamel surface. In 1 individual the microbial deposits were dominated by large bacteria, the ultrastructure of which conformed to the description of Stomatococcus mucilaginosus. These findings may partly explain pronounced individual variations in the rate of caries lesion development and progression in vivo.

Short-Chain Fatty Acids in the Normal Human Feces

The short-chain fatty acids ( SCFAs ) have been studied in the feces of 20 healthy subjects--10 methane excretors and 10 non-methane excretors. The analytical procedure included homogenization of fecal samples followed by vacuum distillation and subsequent gas chromatography. This method for analysis of fecal SCFAs showed recoveries of the individual acids from 90% to 109% and coefficients of variation for the inter-assay reproducibility from 6.0% to 19.7%, highest for those acids present in the smallest concentrations. There was no difference in the concentrations or relative compositions of SCFAs between methane-excreting subjects and non-methane-excreting subjects. The concentrations of SCFAs , given as mmol/kg feces (wet weight), were (median and range): total, 76.8 (27.9-187.7); acetic acid, 37.4 (12.8-103.4); propionic acid, 12.5 (4.5-27.8); i-butyric acid, 2.2 (0.7-3.8); n-butyric acid, 12.4 (4.0-53.0); i-valeric acid, 3.2 (0.8-5.9); n-valeric acid, 2.4 (0.6-3.8) and n-caproic acid, 0.5 (0.0-3.6). The study shows that the SCFAs are quantitatively the most important anions in the feces of healthy subjects. The pronounced individual variations in the concentrations of SCFAs are real biological variations and cannot be explained by methodological variations.

Space motion sickness

Space motion sickness, presumably triggered by sudden entry into a weightless environment, occurred with unexpected frequency and severity among astronauts who flew the Skylab missions. Recovery from symptoms was complete within 3–5 days, and as revealed by the Skylab M131 Human Vestibular Function Experiment, all crewmembers were immune to experimentally induced motion sickness after mission day 8. This syndrome has been recognized as a possible threat to the early mission well-being and operational efficiency of at least some individuals who will fly space missions in the future. The causes of space motion sickness are not clearly understood, nor have satisfactory methods been identified to date for its prediction, prevention and treatment. In order to minimize the potential impact of this syndrome on Space Shuttle crew operations the National Aeronautics and Space Administration has organized a broad program of inter-disciplinary research involving a large number of scientists in the United States. Current research on the etiology of space motion sickness is based to a large extent on the so called sensory conflict theory. Investigations of the behavioral and neurophysiological consequences of intralabyrinthine, as well as intermodality sensory conflict are being performed. The work in this area is being influenced by the presumed alterations that occur in otolith behavior in weightlessness. In addition to sensory conflict, the possible relationship between observed cephalad shifts of body fluids in weightlessness and space motion sickness is being investigated. Research to date has failed to support the fluid shift theory. Research underway to identify reliable test methods for the prediction of susceptibility to space motion sickness on an individual basis includes attempts to (a) correlate susceptibility in different provocative environments; (b) correlate susceptibility with vestibular and non-vestibular response parameters, the latter including behavioral, hemodynamic and biochemical factors and (c) correlate susceptibility with rate of acquisition and length of retention of sensory adaptation. Controlled studies are also being performed during parabolic flight as a means of attempting to validate predictive tests for susceptibility to this syndrome. Research to develop new or improved countermeasures for space motion sickness is underway in two primary areas. One of these involves anti-motion sickness drugs. Significant achievements have been realized with regard to the identification of new highly efficacious drug combinations, dose levels and routes of administration. Although pronounced individual variations must be accounted for in selecting the optimum drug and dose level, combinations of promethazine plus ephedrine or scopolamine plus dexidrine are presently the drugs of choice. Work is also underway to identify side effects associated with anti-motion sickness drug use and to identify new drugs which may selectively modify activity in central neural pathways involved in motion sickness. In addition to research on drugs, efforts are being made to develop practical vestibular training methods. Variables which influence rate of acquisition of adaptation, length of retention of adaptation and transfer of protective adaptation to new environments are being evaluated. Also, included in this area is the use of biofeedback and autogenic therapy to train individuals to regulate autonomic responses associated with motion sickness. While valuable new knowledge is expected to evolve from these combined research programs, it is concluded that the final validation of predictive tests and countermeasures will require a series of controlled space flight experiments.

Loci, structure and function of contact chemical sensilla in haematophagous tabanids (Diptera).

In the present study the females of Chrysops vittatus Wiedemann, Hybomitra lasiophthalma Macquart and Tabanus lincola Fabricius were observed to contain taste sensilla only on the ventro-lateral surface of the foretarsi and the aboral margin of the labella. These sensilla were medium-sized, curvaceous, blunt-tipped and were sensitive to sucrose stimulation only at the tip. Four types of labellar trichodes (A, B, C, and D types) that differed in their morphology and size were identified on the aboral margin of the labella of C. vittatus. Two other types (E and F) were identified on the anterior aspect of the labella. Pronounced individual variations were observed in C. vittatus with regard to the number of sensilla. Differences were also noticed in the number of sensilla present on the left and right halves of the labellum. Discussion is presented on the interrelationship of taste sensilla in relation to feeding behavior. Extension of the proboscis was the index of positive tarsal stimulation, and the opening of the labellar lobes in an extended proboscis the criterion of positive labellar stimulation.

The Individual Variability in Respiration. Elucidated by Determination of the Excitability of the Respiratory Centre

Summary.Individual variations in the excitability of the respiratory centre are considerable. Numerically expressed — by a special method — the excitability coefficients of 36 patients (convalescents after melancholia) were found to vary from 12.2 to 34.4, and from 11.6 to 41.3, in 26 normal subjects. Correspondingly, pronounced individual variations were ascertained in respect of rate and depth of respiration, of ventilation, and of CO2 tension in alveolar air — in the cases of 26 normal subjects and 36 patients.