An influence of afterhyperpolarization on the pattern of motoneuronal rhythmic activity.

Motoneuronal spike trains were generated according to a simple model assuming algebraical summation of the afterhyperpolarization (AHP) curve and noisy synaptic inflow. An influence of various model parameters on the relationship between standard deviation (SD), sigma, of interspike intervals (ISIs) and their mean value, Tm, was studied. A typical sigma(Tm) relationship resembled those obtained experimentally and consisted of two parts: a short-interval part with constant sigma and a long-interval part where sigma increased linearly with increasing ISI. It is concluded that the placement of the range of transition between short- and long-interval parts of the plot depends on the properties of the motoneuron and not on those of the synaptic inflow. The break-point interval of the plot is correlated with the AHP duration but is shorter than it. Further, not only are the curves for shorter AHP durations shifted towards shorter ISIs, but they also have lower SDs at their short-interval parts.     

Administration of gonadotropin-releasing hormone during metoestrus in cattle: influence on luteal function and cycle length

Gonadotropin-releasing hormone (GnRH) has been used to warrant the success of artificial insemination by accurately timing occurrence of ovulation. In practical conditions, GnRH may be administered too late, after ovulation, with an eventual reduction in pregnancy rate. The aim of this study was to investigate whether GnRH administration after ovulation would have a negative effect on luteal function.Three cows and six heifers of the Finnish Ayrshire breed were used. Oestruses were synchronised. After detection of ovulation, one of the following treatments was implemented: gonadorelin (250 microg, i.m.) at either 0-24h (T1) or 24-48h (T2) post-ovulation or control (no gonadorelin, C). Every animal was assigned once to each of these three manipulations. Ultrasonography was performed on days 1, 4 or 5, 7 or 8, 11 or 12, 14 or 15 post-ovulation and daily from the beginning of the next oestrous signs until ovulation (day 0=day of ovulation). Blood samples for progesterone (P(4)) determinations were collected daily from day 1 after the occurrence of ovulation until recording of the next oestrus. Administration of GnRH during metoestrus did not induce ovulation of either large or small follicles and, thus, no accessory corpora lutea (CL) were formed. In T1, on day 14 or 15, the diameter of CL was 1.3+/-0.3mm smaller than in C (P<0.01), but no differences were found either on days 11 or 12 or on the same days of the T2 and C treatments. No significant differences in levels or profiles of P(4) curves were found between GnRH treatments and control. Neither had the treatments any effects on the length of the oestrous cycle. In conclusion, GnRH treatment during metoestrus does not seem to alter subsequent luteal function and, thus, this does not explain previous reports of reduced fertility post-treatment.     

Disorder influence on linear dichroism analyses of smectic phases

Linear dichroism, the unequal absorption of parallel and perpendicular linear polarized light, is often used to determine the anisotropic ordering of rodlike polymers in a smectic phase, such as helices in a lipid bilayer. It is a measure of two properties of the sample: 1), orientation of the chromophore transition dipole moment (TDM) and 2), disorder. Since it is the orientation of the chromophore TDM that is needed for high resolution structural studies, it is imperative to either deconvolve sample disorder, or at a minimum, estimate its effect upon the calculated TDM orientation. Herein, a rigorous analysis of the effects of disorder is undertaken based on the recently developed Gaussian disorder model implemented in linear dichroism data. The calculation of both the rod tilt and rotational pitch angles as a function of the disorder and dichroism, yield the following conclusions: Disorders smaller than 5 degrees have a vanishingly small effect on the calculated polymer orientation, whereas values smaller than 10 degrees have a negligible effect on the calculated parameters. Disorders larger than 10 degrees have an appreciable effect on the calculated orientational parameters and as such must be estimated before any structural characterization. Finally the theory is tested on the HIV vpu transmembrane domain, employing experimental mosaicity measurements from x-ray reflectivity rocking scans and linear dichroism.     

Cellular function and molecular structure of ecto-nucleotidases

Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ecto-nucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5'-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.     

Cellular and molecular analyses of olfactory behavior in C. elegans

C. elegans responds to and discriminates among a large number of volatile and water-soluble chemicals using a few defined chemosensory neurons. The functions of individual sensory neurons have been defined by cell killing experiments, and genes required for responses to subsets of chemicals have been identified. C. elegans has several large families of putative chemosensory receptor genes, and one of these genes has been demonstrated to encode a receptor for a specific odorant. Current work is aimed at identifying additional components of chemosensory neuron development and function.     

Cellular and molecular analyses of vascular tube and lumen formation in zebrafish

Tube and lumen formation are essential steps in forming a functional vasculature. Despite their significance, our understanding of these processes remains limited, especially at the cellular and molecular levels. In this study, we analyze mechanisms of angioblast coalescence in the zebrafish embryonic midline and subsequent vascular tube formation. To facilitate these studies, we generated a transgenic line where EGFP expression is controlled by the zebrafish flk1 promoter. We find that angioblasts migrate as individual cells to form a vascular cord at the midline. This transient structure is stabilized by endothelial cell-cell junctions, and subsequently undergoes lumen formation to form a fully patent vessel. Downregulating the VEGF signaling pathway, while affecting the number of angioblasts, does not appear to affect their migratory behavior. Our studies also indicate that the endoderm, a tissue previously implicated in vascular development, provides a substratum for endothelial cell migration and is involved in regulating the timing of this process, but that it is not essential for the direction of migration. In addition, the endothelial cells in endodermless embryos form properly lumenized vessels, contrary to what has been previously reported in Xenopus and avian embryos. These studies provide the tools and a cellular framework for the investigation of mutations affecting vasculogenesis in zebrafish.     

The influence of age on human pancreatic growth hormone releasing hormone stimulated growth hormone secretion

63 non-obese healthy subjects aged 18 to 95 years were investigated for age-dependence of GHRH-stimulated GH-secretion. In addition, priming of GH-secretion with three oral doses of propranolol (3 x 80 mg, the last dose 2 hours prior to the second GHRH-bolus) was carried out in 15 subjects below 40 years and 13 subjects older than 70 years. We found that mean maximal incremental GH-levels were inversely correlated with chronological age (r = -0.44, P = 0.001) of the probands. Propranolol premedication caused a significant rise of both basal and peak GHRH-induced relative increases in all subjects tested, whereas GHRH-induced relative increases of GH remained unchanged. In a well selected group of non-obese healthy subjects stimulated GH-secretion is found to undergo an aging process that is supposed to be of pituitary and suprapituitary origin. Priming GH-secretion with a beta-Blocker is possible both in young and very old healthy subjects and is likely to affect the basal GH secretory tone and not GHRH-stimulated GH-secretion.     

Genetic and molecular analyses of motoneuron development

Motoneurons have distinct identities and muscle targets. Recent classical and molecular genetic studies in flies and vertebrates have begun to elucidate how motoneuron identities and target specificities are established. Many of the same molecules participate in the guidance of both vertebrate and fly motor axons. It is less clear, however, whether the same molecular mechanisms establish vertebrate and fly motoneuron identities.     

Effects of growth hormone on cognitive function

Whether growth hormone deficiency (GHD) and/or treatment in childhood and adolescence influences cognitive outcome in children with GHD or girls with Turner syndrome (TS) is controversial. Previous studies also suggest that quality of life (QoL) is reduced in adults with GHD, particularly in the areas of social isolation and fatigue. Baseline QoL scores were significantly lower in patients with GHD than in the general population of the same age, gender, and nationality. Unfortunately, few data are available describing QoL in children with GHD. TS is a genetic disorder characterized by short stature, gonadal dysgenesis, and a particular neurocognitive profile of normally developed language abilities (particularly verbal intelligence quotients) and impaired visual-spatial and/or visual-perceptual abilities. This study evaluated the effects of GH treatment on neurocognitive function in girls with TS who were enrolled in a long-term, double-blind, placebo-controlled trial of the effects of GH treatment on final adult height. Treatment duration ranged from 1 to 7 years. The major result of this study was the absence of GH treatment effects on cognitive function in girls with TS. GHD and/or treatment in childhood and adulthood influences cognitive and/or QoL outcomes in some but not all studies. This study did not support a role for GH in influencing the characteristic nonverbal neurocognitive deficits associated with TS. However, evaluation of QoL should be a part of the routine clinical management of patients with GHD or TS.     

The influence of ovarian factors on the somatostatin-growth hormone system during the postnatal growth and sexual development in lambs

The aim of the study was to elucidate the effects of ovarian hormones on somatostatin in the hypothalamic neurons and growth hormone (GH) secretion during the postnatal growth and development of sheep. The study was performed on 9-week-old (infantile) lambs that were ovary-intact (OVI) or ovariectomized (OVX) at 39 days of age, and on 16-week-old (juvenile) lambs that were OVI or OVX at 88 days of age. Hormones in neurons and somatotropic cells were assayed with immunohistochemistry and radioimmunoassay. Following ovariectomy, immunoreactive somatostatin was more abundant (p<0.05) in the hypothalamus of infantile lambs, whereas in juvenile lambs it was more abundant (p<0.05) in the periventricular nucleus but reduced (p<0.01) in the median eminence. In contrast to somatostatin in the hypothalamus, the content of immunoreactive GH in the hypophysis was less in OVX infantile lambs, but greater in OVX juvenile lambs (p<0.05). Basal blood serum concentrations of GH were greater (p<0.05) in OVX infantile lambs, whereas in OVX juvenile lambs, mean and basal concentrations of GH and amplitude of GH pulses were less than in OVI lambs (p<0.05). The postnatal increase in body weight was greatest in middle-late infancy (p<0.01). The body weight did not differ (p>0.05) between OVI and OVX lambs. In conclusion, ovarian factors may inhibit the GH secretion in infantile lambs but enhance the GH secretion in juvenile lambs. Transition to puberty, as related to the growth rate, appears to be due mainly to change in gonadal influence on the somatostatin neurosecretion. A stimulation of somatostatin output in the median eminence by gonadal factors in infancy is followed by a stimulation of somatostatin accumulation after infancy. Thus, ovarian factors modulate mechanisms within the somatotropic system of lambs to synchronize the somatic growth with sexual development.