Showing papers by "Uppsala University published in 1992"

A global biome model based on plant physiology and dominance, soil properties and climate

Abstract: A model to predict global patterns in vegetation physiognomy was developed from physiological considera- tions influencing the distributions of different functional types of plant. Primary driving variables are mean coldest- month temperature, annual accumulated temeprature over 5"C, and a drought index incorporating the seasonality of precipitation and the available water capacity of the soil. The model predicts which plant types can occur in a given environment, and selects the potentially dominant types from among them. Biomes arise as combinations of domi- nant types. Global environmental data were supplied as monthly means of temperature, precipitation and sunshine (interpolated to a global 0.5" grid, with a lapse-rate correc-

A meta-analysis of thoracic radiotherapy for small-cell lung cancer.

Abstract: Background. In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. Methods. We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. Trials that included only patients with extensive disease were excluded. Results. The meta-analysis included 13 trials and 2140 patients with limited disease. A total of 433 patients with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up peri...

Fatty acid content and chemical composition of freshwater microalgae1

Abstract: Fatty acid (FA), total lipid, protein, amino acid, carbon, nitrogen, and phosphorus content was analyzed in 24 samples of freshwater microalgae. The samples originated from batch, continuous, or mass cultures in various growth phases and from net samples from lakewater. FA were analyzed quantitatively by using an internal standard in a GLC system and expressed as mg·g−1 dry weight (DW). The FA of one group of blue-greens (e.g. Oscillatoria and Microcystis) were similar to those of the greens with higher amounts of 18C acids of the ω3 type compared to the ω6 type, whereas the other group (e.g. Anabaena and Spirulina) contained mostly ω6 acids. The flagellates, a taxonomically diverse group, were characterized by high amounts of long-chained (20–22 C) polyunsaturated FA (PUFA), particularly of the ω3 type. The ω3/ω6 ratio appears to be highest in algae in the exponential growth phase. The increased lipid content in stressed algae was mostly due to increased saturated fatty acids and ω6 acids, whereas the valuable ω3 acids were unchanged or even decreased. Amino acid composition (% of total amino acids) did not vary much betaken species, but when analyzed quantitatively (mg-g−1 DW), varied considerably between species and within species in different growth phases. The nitrogen and phosphorus contents were variable in all three algal groups. The relationship between PUFA and phosphorus content differed among the algal groups. The data suggest that PUFA in the phospholipids consist mostly ω3 acids.

Female swallow preference for symmetrical male sexual ornaments.

Abstract: Many secondary sexual characters are supposed to have evolved as a response to female choice of the most extravagantly ornamented males, a hypothesis supported by studies demonstrating female preferences for the most ornamented males. Comparative studies of elaborate feather ornaments in birds have shown that (1) ornaments have larger degrees of fluctuating asymmetry (small, random deviations from bilateral symmetry caused by an inability of individuals to cope with environmental and genetic stress during development of a character) than other morphological traits, and (2) the degree of fluctuating asymmetry is often negatively related to the size of the ornament. The negative relationship between ornament asymmetry and size suggests that ornament size reliably reflects male quality because the largest secondary sex traits demonstrate the least degree of fluctuating asymmetry. I manipulated tail length and tail asymmetry independently in male swallows (Hirundo rustica) to determine whether ornament size or asymmetry were used as cues in mate choice. Male swallows with elongated, symmetric tails mated earlier, and enjoyed larger annual reproductive success than did males with shortened tails and increased asymmetry. Females therefore prefer large as well as symmetric ornaments, which suggests that females in their mate choice use ornament asymmetry and size as reliable indicators of male quality.

The Agency-Structure Problem in Foreign Policy Analysis

Abstract: The starting point of this article is the argument that scholars of foreign policy—in contrast to international relations theorists—have not sufficiently faced up to the explanatory implications of the agency-structure issue in the philosophy of social science. This claim is discussed with reference to four fundamental perspectives in foreign policy analysis, defined in terms of ontological and epistemological assumptions regarding the nature of social order and individual action . Taking its cue primarily from recent philosophical discussions within sociology and social theory, it proposes a metatheoretical framework based on a dynamic conception of the interplay over time between interpretative, purposive agents and a structural domain defined in terms of both constraining and enabling properties. On the basis of this suggested solution to the agency-structure problem, the article subsequently elaborates an explanatory framework premised on a morphogenetic conception of the contextually bound nature of the foreign policy behavior of states, arguing that this reconceptualization can incorporate not only (1) certain rationality assumptions of action, (2) psychological-cognitive explanatory approaches, and (3) the role, broadly speaking, of situational-structural factors, but also (4) an institutional perspective combined with (5) comparative case study analysis.

Function and evolution in the NGF family and its receptors

Abstract: The gene family of neurotrophins includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Recently, neurotrophin-5 (NT-5), a possible mammalian homologue to NT-4 described in the frog Xenopus, has been cloned in man and rat. The neurotrophins stimulate survival and differentiation of a range of target neurons by binding to cell surface receptors. The structure of NGF has recently been clarified from crystallographic data. The similarities between the different neurotrophins are substantial with the variable regions, giving specificity to each of the family members, being localized to some exposed loop regions. Low-affinity binding (Kd of 10−9 M) of all tested neurotrophins is mediated via a 75 K glycoprotein (LNGFR) that has been cloned and characterized. A 140 K tyrosine protein kinase encoded by the proto-oncogene trk has been found to bind NGF with high affinity (Kd of 10−11 M) and to evoke the cellular neurotrophic responses. In addition, a protein encoded by the trk-related gene trkB has been shown to bind BDNF. Recently, a third member of the trk family, trkC, has been cloned and demonstrated to function as a high-affinity receptor for NT-3. The expression of trk and LNGFR mRNA are co-localized in the rat brain to the medial septal nucleus and the nucleus of Broca's diagonal band containing the NGF-responsive magnocellular cholinergic neurons projecting to hippocampus and cerebral cortex. In sharp contrast, the pattern of expression of trkB is widely spread in many areas of the cortex as well as lateral septum. The trkB protein might serve general functions in large areas of the cortex. Site-directed mutagenesis and expression of recombinant chimaeric neurotrophin proteins have made it possible to localize a likely region for the interaction between NGF and the LNGFR. This region could be altered, resulting in the total loss of LNGFR binding by the mutant NGF protein without affecting the binding to the trk receptor which was sufficient for the full biological activity. Cladistic analysis of likely phylogenies within the neurotrophins shows BDNF and NT-4 to be most closely related whereas NGF may be the sister group to NT-3, BDNF, and NT-4. Neurotrophins offer obvious clinical possibilities for treatment of neurodegenerative diseases. © 1992 Wiley-Liss, Inc.

Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report).

Abstract: Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of 11C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.

Translational accuracy and the fitness of bacteria

Abstract: There are two aspects of the relationship between translational accuracy and the fitness of bacteria that I hope have been clarified in this review. One is that the impact of translational errors on the fitness of bacteria depends very much on nutritional conditions. It would seem that bacterial populations have the capacity to respond to different growth opportunities by the selection of suitable variants. It is particularly surprising how few mutations seem to be required to transform a slowly growing natural isolate with inefficient as well as inaccurate ribosomes into a growth-optimized laboratory strain. It would not be suprising if the selection of the slow, natural isolate phenotype under starvation conditions is equally facile. Another aspect of the accuracy-fitness relationship worth emphasizing is the strong impact of processivity errors and the weak impact of missense errors on the structures of proteins as well as on the growth of cells. What has been learned about translation mechanisms up to now is really only a preliminary to what remains to be discovered about the movements of tRNA, mRNA, and ribosomal subunits that support the processivity of translation. It would be very useful to have more direct methods at hand with which to study these movements. Likewise, the availability of methods to measure processivity errors in natural isolates would help to round out our view of the variability of the ribosomal mechanisms in nature.

Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the beta-cell function.

Abstract: The aim of the present study was to clarify whether prolonged in vitro exposure of human pancreatic islets to high glucose concentrations impairs the function of these cells. For this purpose, islets isolated from adult cadaveric organ donors were cultured for seven days in RPMI 1640 medium supplemented with 10% fetal calf serum and containing either 5.6, 11, or 28 mM glucose. There was no glucose-induced decrease in islet DNA content or signs of morphological damage. However, islets cultured at 11 or 28 mM glucose showed a 45 or 60% decrease in insulin content, as compared to islets cultured at 5.6 mM glucose. Moreover, when such islets were submitted to a 60-min stimulation with a low (1.7 mM) followed by a high (16.7 mM) concentration of glucose, the islets cultured at 5.6 mM glucose showed a higher insulin response to glucose than those of the two other groups. Islets cultured at the two higher glucose concentrations showed increased rates of insulin release in the presence of low glucose, and a failure to enhance further the release in response to an elevated glucose level. Islets cultured at 28 mM glucose showed an absolute decrease in insulin release after stimulation with 16.7 mM glucose, as compared to islets cultured at 5.6 mM glucose. The rates of glucose oxidation, proinsulin biosynthesis, and total protein biosynthesis were similar in islets cultured at 5.6 or 11 mM glucose, but they were decreased in islets cultured at 28 mM glucose. These combined results suggest that lasting exposure to high glucose concentrations impairs the function of human pancreatic islets.

The NMDA-receptor antagonist CPP abolishes neurogenic ‘wind-up pain’ after intrathecal administration in humans

Abstract: Involvement of the NMDA receptor system in the transmission of nociceptive information, including the development of central sensitization and a wind-up phenomenon, has increased interest in NMDA-receptor antagonists as antinociceptive drugs. This case report describes the use of an NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) in a carefully selected patient with severe and intractable neurogenic pain in her left leg. The pain syndrome had components of a continuous deep pain, an allodynia, and a wind-up-like component, including afterdischarge and spread of painful sensations outside the territory of the injured nerve. After intrathecal (i.t.) administration of 200 nmol of CPP the continuous deep pain component and allodynia were unchanged, but the following 'wind-up' phenomenon with afterdischarge and spread of the pain sensation in the left half of the body was completely abolished. Another 500 nmol of CPP administered over 2 h did not improve pain relief. Pain thresholds for heat and cold stimulation, measured with a Marstock thermostimulator, did not change. There was no effect on blood pressure, heart rate, sensitivity, reflexes, coordination or motor performance. Psychotomimetic ketamine-like side effects developed 4 h after the last injection of CPP and were probably due to rostral spread of CPP. These early experiences with i.t. administration of NMDA-receptor antagonists to humans indicate that the NMDA-receptor system plays an important role in neurogenic pain and that antagonizing this system may be a useful way to obtain better pain control although psychotomimetic side effects due to rostral spread may be a problem.

A single mutation affects both N-acetylglucosaminyltransferase and glucuronosyltransferase activities in a Chinese hamster ovary cell mutant defective in heparan sulfate biosynthesis.

Abstract: Mutants of Chinese hamster ovary cells have been found that no longer produce heparan sulfate. Characterization of one of the mutants, pgsD-677, showed that it lacks both N-acetylglucosaminyl- and glucuronosyltransferase, enzymes required for the polymerization of heparan sulfate chains. pgsD-677 also accumulates 3- to 4-fold more chondroitin sulfate than the wild type. Cell hybrids derived from pgsD-677 and wild type regained both transferase activities and the capacity to synthesize heparan sulfate. Two segregants from one of the hybrids reexpressed the dual enzyme deficiency, the lack of heparan sulfate synthesis, and the enhanced accumulation of chondroitin sulfate, suggesting that all of the traits were genetically linked. These findings indicate that the pgsD locus may represent a gene involved in the coordinate control of glycosaminoglycan formation.

The effect of MK-801 on cortical spreading depression in the penumbral zone following focal ischaemia in the rat.

Abstract: Cortical spreading depression (CSD) is a transient depression of neuronal activity that spreads across the cortical surface. In the present studies, we have investigated CSD activity in the penumbral zone following permanent middle cerebral artery (MCA) occlusion in the rat (n = 16/group), using double-barreled Ca(2+)-sensitive microelectrodes. Measurements of CSD activity were made for 3 h in each animal. During this time, a varying number of spontaneous CSDs were seen in the control group (total was 30, with a range of 0-7/rat). These CSDs were of varying duration: "small" (approximately 1 min) and "big" (5-45 min) CSDs. During a CSD, the extracellular [Ca2+] decreased to 0.11 +/- 0.07 mM (mean +/- SD). After 3 h, the extracellular [Ca2+] in the cortex (penumbral zone) was either normal (10/16 rats) or lowered to 0.5 mM (2/16 rats) or to 0.1 mM (4/16 rats). In the caudate nucleus (ischaemic core area), all rats had an extracellular [Ca2+] of approximately 0.1 mM when measured after the 3 h recording period. Neuropathological evaluation of the brains of the animals, which had been allowed to survive for 24 h after MCA occlusion, revealed ischaemic damage in the dorsolateral cortex and caudate nucleus. Administration of the noncompetitive NMDA antagonist, MK-801 (3 mg/kg i.p.), 30 min after MCA occlusion resulted in 24 and 29% reductions in the volume of hemispheric and cortical damage, respectively, which was highly significant (p less than 0.0001); no protection was seen against caudate damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Democracy and Development

Abstract: This book is a thorough investigation into the requisites of democracy. Based on data from 132 sovereign states of the Third World, it first establishes a scale to measure the level of democracy existing in these countries. The author discusses various interpretations of the meaning of political democracy, and emerges with a specification of its essential elements which includes such elements as the holding of elections to central decision-making organs, and the maintenance of certain fundamental political liberties. Theories concerning the requisites of democracy are then examined in order to explain the manifest differences in the level of democracy among the states of the Third World. The author employs statistical techniques including regression analysis to test theories related to socio-economic conditions, demographic and cultural factors, and institutional arrangements. This book thus provides a wide-ranging examination both of the elements which constitute democracy, and of the factors which explain its varying prevalence.

Ancestral Areas: A Cladistic Reinterpretation of the Center of Origin Concept

Abstract: The search for centers of origin has fallen into disrepute because of unfounded assumptions and spurious criteria. Nevertheless, a proper approach to understanding ancestral areas would enhance the study of the natural history of organisms. If there is reason to assume that a group originally had a more restricted distribution than it has today, a method for estimating that ancestral distribution is warranted. I describe a cladistic procedure for approximating ancestral areas of individual groups from the topological information in their area cladograms. Each area is treated as a single character, which may be optimized onto the cladogram using either forward or reverse Camin-Sokal parsimony (...)

Nicotinic and muscarinic subtypes in the human brain: changes with aging and dementia.

Abstract: Different effects of normal aging on muscarinic and nicotinic receptor subtypes were observed in postmortem brain tissue from different regions of the human brain. A significant decrease in Ml and M2 receptors was found in cerebral cortex, while the Ml and especially the M2 receptors increased with age in the thalamus. A similar pattern of changes was also observed when using (−)3H-nicotine as ligandfor nicotinic receptors in the cortex and thalamus. No significant changes in nicotinic receptor binding were observed with age in the cortex or thalamus, when using 3H-acetylcholine as ligand. Nicotinic and muscarinic receptors in the brain are not equally affected in dementia disorders. A marked loss of high affinity nicotinic receptors was observed in cortical tissue from patients with Alzheimer's disease and with multi-infaret dementia (MID). The muscarinic receptors were (both Ml and M2) increased in Alzheimer cortical tissue while they were decreased in MID.

Predatorial borings in late precambrian mineralized exoskeletons.

Abstract: The late Precambrian tube-forming Cloudina, the earliest known animal to produce a mineralized exoskeleton, shows evidence of having been attacked by shell-boring organisms. Of more than 500 tubes from Shaanxi Province, China, 2.7% have rounded holes 40 to 400 micrometers in diameter. The relation between the size of the holes and the width of the bored tubes suggests that the attacking organism was a predator, selecting its prey for size. If true, this would be the oldest case of predation in the fossil record and would support the hypothesis that selection pressures from predation was a significant factor in the evolution of animal skeletons around the Precambrian-Cambrian boundary.

Dynamics of savanna ecosystems

Abstract: Theories concerning the factors involved in the dynamics of savannas, particularly the tree-grass interface, are reviewed. Emphasis is put on factors related to soil moisture, soil nutrients, fire and large herbivores. The distinction be- tween external (independent) and internal (dependent, interac- tive) environment is discussed and it is explained how this distinction is affected by the scale of observation.

Laboratory determination of chemotherapeutic drug resistance in tumor cells from patients with leukemia, using a fluorometric microculture cytotoxicity assay (FMCA).

Abstract: An automated fluorometric microculture cytotoxicity assay (FMCA) based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein was employed for chemotherapeutic-drug-sensitivity testing of tumor-cell suspensions from patients with leukemia. Fluorescence was linearly related to cell number, and reproducible measurements of drug sensitivity could be performed using fresh or cryopreserved leukemia cells. A marked heterogeneity with respect to chemotherapeutic drug sensitivity was observed for a panel of cytotoxic drugs tested in 43 samples from 35 patients with treated or untreated acute and chronic leukemia. For samples obtained from patients with chronic lymphocytic and acute myelocytic leukemia, sensitivity profiles for standard drugs corresponded to known clinical activity and the assay detected primary and acquired drug resistance. Individual in vitro/in vivo correlations indicated high specificity with respect to the identification of drug resistance. The results suggest that the FMCA may be a simple and rapid method for in vivo-representative determinations of chemotherapeutic drug resistance in tumor cells obtained from patients with leukemia.

Inverse melting transition and evidence of three-dimensional cubatic structure in a block-copolymer micellar system.

Abstract: Structural studies on aqueous solutions of PEO-PPO-PEO block copolymers show three phases as the temperature is varied. At low T, the tri-block units are dissolved Gaussian chains. As T is increased still more unimers aggregate in micelles, until a volume fraction of 0.52 is reached. The micelles then crystallize in a body-centered-cubic lattice. Upon the application of a small shear, the high-T polycrystalline phase abruptly transforms into a single crystal, characterized by only quasi-long-range order in bond length, but true long-range correlations in the bond angle.

Is Abdominal Body Fat Distribution a Major Explanation for the Sex Difference in the Incidence of Myocardial Infarction? The Study of Men Born in 1913 and The Study of Women, Göteborg, Sweden

Abstract: The authors considered whether the difference in body fat distribution between men and women, measured as waist:hip ratio, might explain part of the sex difference in coronary heart disease incidence in prospective population studies of 1,462 women and 792 men. In these studies, conducted in Sweden, men were found to have about four times higher odds for coronary heart disease than women during a 12-year follow-up period (men, 1967 to 1979; women, 1968-1969 to 1980-1981). Controlling for differences in blood pressure, serum cholesterol, smoking, and body mass index only marginally altered the magnitude of the male-female difference. When waist:hip ratio, which predicted coronary heart disease rates in both sexes, was also considered, the sex difference in coronary heart disease risk was significantly reduced and virtually disappeared (odds ratios = 1.0-1.1; nonsignificant). The findings suggest that body fat distribution or a factor highly correlated with waist:hip ratio (genetic, hormonal, or behavioral) may help to explain the sex differences in coronary heart disease.

Analysis of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrins in cell--collagen interactions: identification of conformation dependent alpha 1 beta 1 binding sites in collagen type I.

Abstract: Integrins can mediate the attachment of cells to collagen type I. In the present study we have investigated the possible differences in collagen type I recognition sites for the alpha 1 beta 1 and alpha 2 beta 1 integrins. Different cyanogen bromide (CB) fragments of the alpha 1 (I) collagen chain were used in cell attachment experiments with three rat cell types, defined with regard to expression of collagen binding integrins. Primary rat hepatocytes expressed alpha 1 beta 1, primary rat cardiac fibroblasts alpha 1 beta 1 and alpha 2 beta 1, and Rat-1 cells only alpha 2 beta 1. All three cell types expressed alpha 3 beta 1 but this integrin did not bind to collagen--Sepharose or to immobilized collagen type I in a radioreceptor assay. Hepatocytes and cardiac fibroblasts attached to substrata coated with alpha 1(I)CB3 and alpha 1(I)CB8; Rat-1 cells attached to alpha 1(I)CB3 but only poorly to alpha 1(I)CB8-coated substrata. Cardiac fibroblasts and Rat-1 cells spread and formed beta 1-integrin-containing focal adhesions when grown on substrata coated with native collagen or alpha 1(I)CB3; focal adhesions were also detected in cardiac fibroblasts cultured on alpha 1(I)CB8. The rat alpha 1 specific monoclonal antibody 3A3 completely inhibited hepatocyte attachment to alpha 1(I)CB3 and alpha 1(I)CB8, as well as the attachment of cardiac fibroblasts to alpha 1(I)CB8, but only partially inhibited the attachment of cardiac fibroblasts to alpha 1(I)CB3. 3A3 IgG did not inhibit the attachment of Rat-1 cells to collagen type I or to alpha 1(I)CB3.(ABSTRACT TRUNCATED AT 250 WORDS)

Copying and sexual selection.

Abstract: Recent studies of a variety of polygynously mating animals indicate that females do not always choose mates independently, but instead may copy the choices of others. Copying could serve either to increase the accuracy of mate assessment or to reduce its costs. It is also likely to affect the intensity of sexual selection.