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PubMed1988

pH-temperature interactions on protein function and hibernation: GDP binding to brown adipose tissue mitochondria.

1. [3H]GDP binding to the uncoupling protein of brown adipose tissue was determined on mitochondria isolated from hibernating European hamsters, at two temperatures, 35 and 15 degrees C, and four values of 25pH (pH corrected to 25 degrees C): 6.4, 6.8, 7.2 and 7.6, encompassing the physiological range of pH. Buffer composition was adjusted to get the same pH-temperature relationship as for mammalian blood, in which this relationship is mainly determined by protein imidazole buffers. 2. The maximal binding capacity was independent both of temperature and pH. The dissociation constant KD was highly pH-dependent, but was independent of temperature when 25pH was held constant. Under these conditions, the uncoupling protein thus fully conserves its regulatory properties over the temperature range studied (eurythermal adaptation). 3. The temperature coefficient of the apparent pK' for the pH effect (-0.012 +/- 0.004) differed significantly from that of GDP terminal phosphoryl group, but not from that of blood protein imidazole buffer groups, in good agreement with the imidazole alphastat theory. 4. The results indicate that GDP reaction with the protein involves an electrostatic binding with a titratable group of the protein, probably a sulfhydryl. 5. pH modulation of the uncoupling of brown adipose tissue mitochondria probably permits a reversible control of thermogenesis in the hibernation cycle, heat dissipation being inhibited by respiratory acidosis in deep hibernation, but facilitated by the hyperventilation of arousal.

Adipose Tissue, Brown↗

PubMed2003

Maternal nutrition, fetal weight, body composition and disease in later life.

Nutritional and hormonal milieu in utero affect fetal growth. Both parties involved have an independent chance, for the occurrence of a developmental error at any stage of their constant developing system. Studies suggest that pregnancy outcome is associated with fetal demand for nutrients and the materno-placental capacity to meet that demand. Failure of the materno-placental supply line to satisfy fetal nutrient requirements results in a range of fetal adaptations and developmental changes, and may lead to permanent alterations in the body's structure and metabolism, and thereby to cardiovascular and metabolic disease in adult life. Changes in the in-utero homeostasis may lead to programming of endocrine and metabolic systems so that feedback systems and reactions are permanently changed. At the present stage, short- and long-term hazards of intra-uterine growth retardation (IUGR) have been identified, but preventive strategies are still lacking. It is unlikely that a single factor will reduce a multi-causal outcome like IUGR. Appropriate population-specific interventions should be a priority.

Adult↗

PubMed2001

[The Heibronnen roll-off shoe. An improved forefoot strain reducing orthosis using biomechanical principles].

To reduce the strain on the middle and forefoot in postoperative and posttraumatic care, we developed a new shoe. It is applied as part of treatment following skeletal or soft tissue surgery in this region and in treatment of the diabetic foot (types I and II). Pedographically, we found the vertex of the roll-off process located at the base of the fifth metatarsal bone, meaning that the foot starts to roll-off at this point while walking. The movement was recorded by a pedobarograph bearing full weight and with the use of one crutch in comparison to the roll-off process in a regular shoe. Results show a reduction of the plantar strain on the forefoot of 70% and of 62% on the Chopart joint while bearing full weight. The use of (forearm-) crutches reduces strain further. The new design of the sole enables the (podiatric) patient to stand and walk in a well-balanced fashion. Since immobilisation of the calf is avoided and muscular function is increased, the risk of thromboembolic complications can be minimized. Four different sizes of the "Strain Minimizing Shoe", including seven modular insoles are available, providing a wide range of individually adapted shoe applications for the patient's foot.

Adult↗

PubMed2006

Spatial contrast sensitivity of birds.

Contrast sensitivity (CS) is the ability of the observer to discriminate between adjacent stimuli on the basis of their differences in relative luminosity (contrast) rather than their absolute luminances. In previous studies, using a narrow range of species, birds have been reported to have low contrast detection thresholds relative to mammals and fishes. This was an unexpected finding because birds had been traditionally reported to have excellent visual acuity and color vision. This study reports CS in six species of birds that represent a range of visual adaptations to varying environments. The species studied were American kestrels (Falco sparverius), barn owls (Tyto alba), Japanese quail (Coturnix coturnix japonica), white Carneaux pigeons (Columba livia), starlings (Sturnus vulgaris), and red-bellied woodpeckers (Melanerpes carolinus). Contrast sensitivity functions (CSFs) were obtained from these birds using the pattern electroretinogram and compared with CSFs from the literature when possible. All of these species exhibited low CS relative to humans and most mammals, which suggests that low CS is a general characteristic of birds. Their low maximum CS may represent a trade-off of contrast detection for some other ecologically vital capacity such as UV detection or other aspects of their unique color vision.

Adaptation, Physiological↗

PubMed1996

Receiver operating characteristic (ROC) analysis of neural code efficacies. I. Graded photoreceptor potentials and data quality.

Nerve cell signals are different in form from the stimuli that evoke them and they exhibit complex spatio-temporal characteristics. This defines a neural coding problem which is addressed by two current theories: Multiple Meaning Theory holds that neural signals contain patterns that make statements about combinations of stimulus properties; the Task Dependence Hypothesis suggests that different features of identical neural signals mediate performance in different behavioral tasks. These coding issues were addressed by investigating the representation of sensory information in the distal nervous system after transduction of visual stimuli into bio-electric signals. The objects of study were light-evoked neural responses which had been intracellularly recorded from single retinula (photoreceptor) cells in Limulus lateral eyes. The efficacies with which sensory information was represented by various candidate neural codes were calculated using receiver operating characteristic (ROC) analyses to provide objective indices. The specific visual problem under investigation was discrimination between light flashes whose intensities differed by a very small amount. A wide range of light adaptation states and relative stimulus intensities were explored. Extremely stringent data quality standards were applied which restricted the investigation to cells whose potentials did not exhibit any statistically significant drift during the hours required for data collection. Seven cellular characterizations were simultaneously monitored to detect drift in a given cell's potentials; these characterizations included the value of the membrane potential and the values of six candidate codes. These codes were: the area under the light-evoked receptor potential (RP), the mean value of the RP, the peak height of the RP, the slope of the onset of the RP, the duration required for the RP to drop from its peak by a given amount, and the duration required for the RP to end. The results were: (1) Light adaptation increases efficacy. (2) Thus, light adaptation trades sensitivity for acuity (as characterized by ROC discriminations). (3) Increasing relative light flash intensity also increases efficacy. (4) The efficacies of the various codes are significantly different and fall in the following order: area > or = peak = mean > or = duration-end = slope = duration-drop. These findings further demonstrate that arbitrary characterizations of stimulus-response relationships are very likely to be incomplete. They particularly indicate that many commonly used and quite conventional neural analysis strategies may substantially under-estimate system performance.

Adaptation, Ocular↗

PubMed1996

Receiver operating characteristic (ROC) analysis of neural code efficacies. II. Optic nerve action potentials and neural transmission.

Action potentials (APs) were intracellularly recorded from eccentric cells (which give rise to optic nerve fibers) in Limulus lateral eyes and their neural coding efficacies were determined over a wide range of light adaptation states and relative stimulus intensities. Extremely stringent data quality procedures were followed to ensure that the results are based on stable preparations. Waveforms which could be compared with those of comparable receptor potentials (RPs) were obtained by constructing plots of the reciprocals of successive interspike intervals, creating instantaneous spike frequency waveforms (ISFWs). Six candidate codes were then measured. They were: the area under the light-evoked ISFW, the mean value of the ISFW, the peak height of the ISFW, the slope of the onset of the ISFW, the duration required for the ISFW to drop from its peak by a given amount, and the duration required for the ISFW to end. Receiver operating characteristic (ROC) analyses were then applied to these coded ISFW values to provide objective indices of AP efficacies in the form of detectability (d') measurements. Several reliable findings were obtained: (1) Both adaptation state and relative intensity affect efficacy. More specifically, the d' values of all codes approach zero, representing chance detectability, when relatively weak flashes are presented in dark-adapted states. (2) Light adaptation produces a sensitivity-acuity tradeoff: as sensitivity decreases in more light-adapted states, detectabilities increase, indicating that ROC-characterized discrimination acuity increases. (3) The AP code efficacy order is similar to but not identical with the efficacy order previously found in photoreceptors: area = peak > or = mean > or = slope = duration-end = duration-drop. The previously measured photoreceptor RP efficacies were quantitatively compared with the present AP data from the optic nerve fiber level, with the following results: (1) All efficacies tend to decline at the more proximal neural level. (2) The decline is code dependent and transmission efficacy falls in this order: peak > area > mean > slope = duration-end = duration-drop. (3) The code which transmits best between photoreceptors and optic nerve fibers (i.e., the peak) differs from the code which has the highest efficacy at the photoreceptor level (i.e., the area); at the more proximal level, these two codes have indistinguishable efficacies. These findings support two conclusions: (1) They further demonstrate that arbitrary characterizations of stimulus-response relationships are very likely to be incomplete. This would be particularly important when, as is often the case in brain research, the mean code alone (i.e., the average firing rate) is used to characterize spike potentials. The present data show that the use of that code would have substantially underestimated detectability had it been used alone. (2) The fact that the code which most completely transmits information between cells is not the code which most completely represents information within a cell leads directly to a possible physiological basis for the existence of multiple neural codes. It particularly leads to the following extension of the Task Dependence Hypothesis of neural coding: Different codes may mediate performance in different behavioral tasks because different codes best serve different neural functions.

Action Potentials↗

PubMed1998

A neuro-mechanical model of legged locomotion: single leg control.

Most models of legged locomotion have concentrated on properties of either the mechanical or the neural system. Here a combined neuro-mechanical model of stepping in a single leg is presented, as the first step in the process of modeling and building a fast and dynamically stable quadruped. It is based on general principles of legged animals with special reference to vertebrates. The mechanical leg was first studied separately in order to take advantage of its inherent mechanical properties and avoid over-control during stepping generation. As a part of the design strategy it uses elastic actuators to increase shock tolerance and energy efficiency. The neural controller consists of a neural phase generator (NPG), a system of fast feedback pathways, and a single control neuron representing descending drive from higher centers in the brain. Sensory information directly influences the movements through the fast feedback pathways, but also entrains the NPG. The NPG has its own description of the state of the leg, which then enables it to set the feedback pathways so that only actions appropriate for the particular stage of the step cycle are undertaken. This preprogramming benefits from the NPG's ability to filter out any inconsistencies or gaps in the afferent input. In this way the model unites the use of central pattern generators and peripheral feedback systems for the generation of stepping movements. The neuro-mechanical system produced stable stepping patterns over a large velocity range and was adaptable to different body weights and landing from varying heights.

Animals↗

PubMed1991

A comparison of apparent mRNA half-life using kinetic labeling techniques vs decay following administration of transcriptional inhibitors.

Several different techniques were used to determine the apparent half-lives of immunoglobulin gamma 2b heavy chain and kappa light chain mRNA's in mouse myeloma 4T001 and a mutant derived from 4T001, i.e., mutant I17. The mutant I17 Ig heavy chain mRNA lacks CH1 and has fused CH2 and CH3 domains resulting in a truncated protein. By all four techniques the Ig heavy chain mRNA from mutant I17 displays a half-life that is approximately 70% the half-life of Ig mRNA in 4T001 cells. However, the absolute values of apparent half-life varied by greater than twofold for both lines among several of the techniques employed. The half-life of Ig gamma 2b mRNA in 4T001 cells was found to be 6.4 h by measuring decay following administration of the adenosine analog DRB to block new mRNA synthesis and 5.7 hr by measuring accumulation in an approach to steady-state labeling protocol. In contrast, the observed Ig mRNA half-lives determined by measuring decay following administration of actinomycin D to block new mRNA synthesis, or in a pulse-chase analysis were 2.9 and 3.8 h, respectively. The apparent half-life for Ig kappa light chain mRNA was the same in the 4T001 and I17 lines using any one technique but the value varied depending on the technique from a high value of 5.9 h following DRB to a low value of 2.4 h with actinomycin decay. Approach to steady-state is theoretically the most accurate method to measure mRNA half-life when that value is less than the doubling time of the cells. Pulse-chase analyses are accurate for measuring mRNA half-life when that value is longer than the effective chase period. Measuring preformed message decay following administration of drugs to block new mRNA synthesis is adaptable over a range of half-lives, but the cells must be shown to retain correct RNA metabolism over the time frame of the experiment. Determining a correct half-life for a particular mRNA may not be feasible using only one method and may, in fact, require several different approaches until a consensus value emerges.

Animals↗

PubMed1996

Soybean agglutinin binding by primary olfactory and primary accessory olfactory projections in different frogs.

Comparing eight species of frogs adapted to habitats ranging from aquatic to arboreal, we observed differences in the affinity of primary olfactory projections to the lectin 'soybean agglutinin'. Particularly pronounced differences exist between Pipa, a frog that rarely leaves the water, and Eleutherodactylus, an arboreal species that does not even utilize aquatic environments for reproduction. We interpret these differences as reflecting specializations to the perception of air-borne vs. water-borne odors.

Animals↗

PubMed1982

Evaluation of mandibular rest position in subjects with diverse dentofacial morphology.

The kinesiometric and electromyographic findings from the evaluation of mandibular resting posture in 30 individuals with diverse vertical dentofacial morphology can be summarized as follows: 1. The RVD and TESP of the mandible are two distinctly different biologically dynamic neuromuscular entities. They differ with respect to their spatial position in that the RVD is 2.6 mm closer to centric occlusion than TESP. 2. The intrapersonal reproducibility of the RVD and TESP at various time intervals predictably demonstrated some biologic variability. 3. The occlusal neuromuscular mechanism apparently maintains a functional tone in the masticatory musculature at the RVD as a result of stimuli from the periodontal mechanoreceptors following tooth contact. 4. A physiologic range of neuromuscular adaptability exists within each diverse morphologic group. Adaptations are apparently mediated by the central nervous system and the musculoskeletal complex. 5. The interocclusal distance at the TESP is inversely related to the vertical dentofacial morphology. 6. Sophisticated computerized morphometrics in combination with the kinesiometric and electromyographic findings of this study demonstrate the dentoalveolar nature of VME and VMD and suggest that correction of these dentofacial deformities by various biologically compatible means will tend to normalize neuromuscular-skeletal relations.

Adolescent↗

PubMed1986

Spatial extent of rod-cone and cone-cone interactions for flicker detection.

Over a large range of light adaptation levels, sensitivity to 25 Hz flicker improves as the light level of the background increases. Using small background discs and annular surrounds, this effect was shown to be mediated by the surround and not the average luminance of the test region, in agreement with recent reports. The effect is due to two types of lateral interaction: at mesopic light levels (from 0.1 to 1.0 td), cone-mediated flicker resolution is enhanced by the stimulation of surrounding rods; at photopic light levels (above 10 td), flicker sensitivity improves with light stimulation of adjacent cones. The spatial zone, or extent, over which the surround contributes to the flicker threshold was measured. The spatial area over which rods influence the cone 25 Hz flicker threshold is larger than the analogous spatial area of cone influence. In the parafovea, at 5 deg eccentricity, cone flicker sensitivity for a 20' spot is influenced by cones in a 1 deg diameter area centered on the spot; the corresponding area of rod influence is about 3 deg. In the fovea, flicker sensitivity for a 10' spot is influenced by cone stimulation in an area of about 20' diameter. Rods which affect foveal flicker sensitivity appear to occupy an annular zone with about a 2 deg outer diameter and 1 deg inner diameter, centered on the fovea.

Adaptation, Ocular↗

PubMed1984

Comparison of automated systems for the cleaning and disinfection of flexible fibreoptic endoscopes.

A comparison of four cleaning and disinfection machines is described. These varied considerably in design and function and although no single machine possessed all the preferred characteristics, cleaning and disinfection, particularly between patients, was substantially improved. Before purchasing a machine it is recommended that the user ensures that it is convenient to operate, effective in removing soil and bacteria, and adaptable to the range of fibrescopes used within the unit. Infections are often caused by Gram-negative bacilli which are particularly difficult to remove manually from moist narrow channels of the fibrescope and perfusion of all channels including the air channel, is, therefore, recommended. Thorough cleaning and disinfection will not only reduce the likelihood of infection but will also reduce channel blockages and the general deterioration of the fibrescope.

Decontamination↗

PubMed1989

Condylar displacement and temporomandibular joint dysfunction following bilateral sagittal split osteotomy and rigid fixation.

In this study changes in intercondylar width (ICW) and intercondylar angle (ICA) that occurred with rigid fixation after bilateral sagittal split osteotomy and mandibular advancement are documented and correlated with temporomandibular (TM) symptoms, magnitude of advancement, and mandibular shape. Even though individual changes occurred, there was no significant difference between the mean preoperative and postoperative ICA and ICW measurements. There was also no significant difference between the preoperative and postoperative incidence of TM pain or clicking. No correlation was found between the magnitude of advancement and the percent change in ICA or ICW, and the mandibular shape did not correlate to changes in ICW. This study suggests that screw osteosynthesis does not significantly change ICA or ICW. The fact that no significant increase in TM symptoms occurred indicates that the changes in condylar position that did occur were within the range of clinical adaptability of the patients.

Bone Screws↗

PubMed1988

The responses recorded in vitro of deep dorsal horn neurons to direct and orthodromic stimulation in the young rat spinal cord.

The electrophysiological properties of 87 neurons in the deep dorsal horn (laminae III-VI) of the rat spinal cord have been investigated in vitro. Two preparations have been used; the transverse spinal cord slice preparation from the third or fourth lumbar segments of 14-16-day-old rats (71 cells) and a hemisected lumbar spinal cord preparation from 10-12-day-old rats (16 cells). The input impedances (range 11-128 M omega), membrane potentials (-67 +/- 8 mV S.D.), action potential amplitude (77 +/- 11.8 mV) duration (1.4 +/- 0.5 ms) and afterpotentials, were effectively identical in the neurons recorded from the two preparations. Neurons in both preparations when activated with long-duration (1-2 s) outward current pulses showed a single steady-state firing range with little adaptation of firing frequency or action potential amplitude. This pattern of responses was unaffected by changing the membrane potential. Orthodromic synaptic activity could be elicited in the neurons by stimulating either the small dorsal root remnants in the slice or the dorsal roots in the hemisected spinal cord. The responses evoked by single stimuli of increasing intensity varied in different neurons in both preparations. The commonest response (32/62) consisted of a short-latency, short-duration composite excitatory postsynaptic potential which generated one or two spikes with no further spiking activity at longer latency when the stimulus intensity was increased beyond threshold. In 20 neurons, graded stimulation produced a graded response with recruitment, at high intensities, of a discharge of action potentials lasting several hundred milliseconds. A small number of cells (4) responded to the single stimulus with a train of action potentials lasting several seconds. Stimulating adjacent dorsal roots in the hemisected cord preparation could evoke quite different responses from the neurons. The heterogeneity of the types of orthodromic responses obtained in both preparations, in spite of the almost uniform intrinsic membrane properties, is likely to reflect differences in the strength, location and type of afferent and interneuronal input to different dorsal horn cells.

Action Potentials↗

PubMed2004

Long-term effects of social stress on brain and behavior: a focus on hippocampal functioning.

In order to study mechanisms involved in the etiology of human affective disorders, there is an abundant use of various animal models. Next to genetic factors that predispose for psychopathologies, environmental stress is playing an important role in the etiology of these mental diseases. Since the majority of stress stimuli in humans that lead to psychopathology are of social nature, the study of consequences of social stress in experimental animal models is very valuable. The present review focuses on one of these models that uses the resident-intruder paradigm. In particular the long-lasting effects of social defeat in rats will be evaluated. Data from our laboratory on the consequences of social defeat on emotional behavior, stress responsivity and serotonergic functionality are presented. Furthermore, we will go into detail on hippocampal functioning in socially stressed rats. Very recent results show that there is a differential effect of a brief double social defeat and repetitive social defeat stress on dendritic remodeling in hippocampal CA3 neurons and that this has repercussions on hippocampal LTP and LTD. Both the structural and electrophysiological changes of principal neurons in the hippocampal formation after defeat are discussed as to their relationship with the maintenance in cognitive performance that was observed in socially stressed rats. The results are indicative of a large dynamic range in the adaptive plasticity of the brain, allowing the animals to adapt behaviorally to the previously occurred stressful situation with the progression of time.

Animals↗

PubMed2005

NO and transcriptional regulation: from signaling to death.

It is nearly 20 years that nitric oxide (NO) entered the scene to become an integral component in understanding physiological and pathophysiological processes ranging from fine-tuned signaling to promoting cell demise. Among multiple activities attributed to NO we find regulation of gene expression. Although there is no evidence for direct NO-responsive DNA elements within promotor regions of eukaryotic genes numerous signaling pathways exist to understand NO-regulated gene expression. A characteristic feature of may transcription factors is their redox sensitivity as well as their low protein abundance in unstressed cells due to efficient 26S proteasomal degradation. Examples comprise the hypoxia inducible factor-1alpha (HIF-1alpha) and p53 (tumor suppressor p53). It became apparent that NO is able to mimic a hypoxic response by stabilizing HIF-1alpha and/or to affect viability decisions by accumulating p53. We will review recent molecular understanding how NO affects stability regulation of HIF-1alpha and p53, considering basic chemical reactions and cellular transducing pathways. Targeting HIF-1alpha and p53 by reactive nitrogen intermediates (RNI) may help to understand a sphere of NO-evoked transcriptional regulation ranging from cellular adaptation to death, i.e. apoptosis with important implications for medicine.

Animals↗

PubMed1999

Preeclampsia: an excessive maternal inflammatory response to pregnancy.

The maternal syndrome of preeclampsia has previously been ascribed to generalized maternal endothelial cell dysfunction. In this review we suggest that the endothelial dysfunction is a part of a more generalized intravascular inflammatory reaction involving intravascular leukocytes as well as the clotting and complement systems. We provide evidence from our recent work and that of others that not only supports this proposal but indicates that such an inflammatory response is already well developed in normal pregnancy and that the differences between normal pregnancy and preeclampsia are less striking than those between the normal pregnant and nonpregnant states. From this we argue that preeclampsia arises when a universal maternal intravascular inflammatory response to pregnancy decompensates in particular cases, which may occur because either the stimulus or the maternal response is too strong. We conclude that there is no specific cause for the disorder, which can be better considered as the extreme end of the range of maternal adaptation to pregnancy. We propose that poor placentation is not the cause of preeclampsia but is a powerful predisposing factor. We predict that a single preeclampsia gene will not be found, nor will either a single specific predictive test or single preventive effective measure be devised. Aspects of the hypothesis are testable, and future work should allow its confirmation or refutation.

Endothelium, Vascular↗

PubMed2002

The SPOT-synthesis technique. Synthetic peptide arrays on membrane supports--principles and applications.

Presented first in 1990 at the 21st European Peptide Symposium in Barcelona, Spain [Frank, R., Güler, S., Krause, S., Lindenmaier, W., 1991. Facile and rapid 'spot synthesis' of large numbers of peptides on membrane sheets. In: Giralt, E., Andreu, D. (Eds.) Peptides 1990, Proc. 21st Eur. Peptide Symp. ESCOM, Leiden, p. 151.], the SPOT-synthesis method opened up countless opportunities to synthesise and subsequently screen large numbers of synthetic peptides as well as other organic compounds arrayed on a planar cellulose support [Tetrahedron 48 (1992) 9217]. Already in 1991, a commercial kit for manual SPOT-synthesis became available through Cambridge Research Biochemicals (CRB, UK), and in 1993, a semi-automated SPOT-synthesiser, the ASP222, was launched by ABIMED Analysen-Technik, Germany. Both made the technique available to many research laboratories, even those not experienced in or equipped for chemistry. Although SPOT-synthesis is not as impressively miniaturised as, e.g. the Affymax photolithographic technique [Science 251 (1991) 767], it fulfils similar demands with the advantage of a reliable and easy experimental procedure, inexpensive equipment needs and a highly flexible array and library formatting. The method permits rapid and highly parallel synthesis of huge numbers of peptides and peptide mixtures (pools) including a large variety of unnatural building blocks, as well as a growing range of other organic compounds. Further advantages are related to the easy adaptability to a wide range of assay and screening methods such as binding, enzymatic and cellular assays, which allow in situ screening of chemical libraries due to the special properties of the membrane supports. Therefore, peptide arrays prepared by the SPOT-technique became quite popular tools for studying numerous aspects of molecular recognition, particularly in the field of molecular immunology.

Combinatorial Chemistry Techniques↗