Rethinking phenotypic plasticity and its consequences for individuals, populations and species.

Much research has been devoted to identify the conditions under which selection favours flexible individuals or genotypes that are able to modify their growth, development and behaviour in response to environmental cues, to unravel the mechanisms of plasticity and to explore its influence on patterns of diversity among individuals, populations and species. The consequences of developmental plasticity and phenotypic flexibility for the performance and ecological success of populations and species have attracted a comparatively limited but currently growing interest. Here, I re-emphasize that an increased understanding of the roles of plasticity in these contexts requires a 'whole organism' (rather than 'single trait') approach, taking into consideration that organisms are integrated complex phenotypes. I further argue that plasticity and genetic polymorphism should be analysed and discussed within a common framework. I summarize predictions from theory on how phenotypic variation stemming from developmental plasticity and phenotypic flexibility may affect different aspects of population-level performance. I argue that it is important to distinguish between effects associated with greater interindividual phenotypic variation resulting from plasticity, and effects mediated by variation among individuals in the capacity to express plasticity and flexibility as such. Finally, I claim that rigorous testing of predictions requires methods that allow for quantifying and comparing whole organism plasticity, as well as the ability to experimentally manipulate the level of and capacity for developmental plasticity and phenotypic flexibility independent of genetic variation.

Pike Esox lucius as an emerging model organism for studies in ecology and evolutionary biology: a review.

The pike Esox lucius is a large, long-lived, iteroparous, top- predator fish species with a circumpolar distribution that occupies a broad range of aquatic environments. This study reports on a literature search and demonstrates that the publication rate of E. lucius research increases both in absolute terms and relative to total scientific output, and that the focus of investigation has changed over time from being dominated by studies on physiology and disease to being gradually replaced by studies on ecology and evolution. Esox lucius can be exploited as a model in future research for identifying causes and consequences of phenotypic and genetic variation at the levels of individuals, populations and species as well as for investigating community processes.

High repetition-rate foam targetry for laser-plasma interaction experiments: Concept and preliminary results.

Foam targets have gained considerable importance over the last decade in laser-matter interaction. They find widespread applications such as in inertial confinement fusion and secondary sources for particles and radiation. At the same time, the advent of high repetition-rate laser systems, be they short-pulse in the tens of femtosecond regime or in the kilo-Joule nanosecond regime, calls for equally high repetition rate targetry systems. A well-established repetition-rate targetry system is the tape target. In this article, we present the successful marriage of a tape target delivery system with 3D-printed foam targets produced by two photon polymerization.

Spatial sorting may explain evolutionary dynamics of wing polymorphism in pygmy grasshoppers.

Wing polymorphism in insects provides a good model system for investigating evolutionary dynamics and population divergence in dispersal-enhancing traits. This study investigates the contribution of divergent selection, trade-offs, behaviour and spatial sorting to the evolutionary dynamics of wing polymorphism in the pygmy grasshopper Tetrix subulata (Tetrigidae: Orthoptera). We use data for > 2800 wild-caught individuals from 13 populations and demonstrate that the incidence of the long-winged (macropterous) morph is higher and changes faster between years in disturbed habitats characterized by succession than in stable habitats. Common garden and mother-offspring resemblance studies indicate that variation among populations and families is genetically determined and not influenced to any important degree by developmental plasticity in response to maternal condition, rearing density or individual growth rate. Performance trials show that only the macropterous morph is capable of flight and that propensity to fly differs according to environment. Mark-recapture data reveal no difference in the distance moved between free-ranging long- and short-winged individuals. There is no consistent difference across populations and years in number of hatchlings produced by long- and shorter-winged females. Our findings suggest that the variable frequency of the long-winged morph among and within pygmy grasshopper populations may reflect evolutionary modifications driven by spatial sorting due to phenotype- and habitat type-dependent emigration and immigration.

Structural and cognitive social capital and depression among older adults in two Nordic regions.

OBJECTIVE: To study the association between structural and cognitive aspects of social capital and depression among older adults in two Nordic regions. METHOD: Data were retrieved from a postal survey targeting older adults aged 65, 70, 75 and 80 years (N=6 838, response rate=64%) residing in the Västerbotten region (Sweden), and the Österbotten region (Finland) in 2010. The associations between structural (measured by frequency of social contact with friends and neighbours) and cognitive (measured by experienced trust in friends and neighbours) aspects of social capital and depression (measured by Geriatric Depression Scale, GDS-4) were tested by logistic regression analyses. RESULTS: Both low structural and cognitive social capital as defined in the study showed statistically significant associations with depression in older adults. Only experienced trust in neighbours failed to show significant association with depression. In addition, being single and being 80 years of age indicated a higher risk of depression as defined by GDS-4. CONCLUSION: The findings underline the connection between adequate levels of both structural and cognitive individual social capital and mental health in later life. They also suggest that the connection differs depending on various network types; the cognitive aspect of relationships between friends was connected to depression, while the connection was not found for neighbours. Further, the oldest age group in the sample (80 years of age) is pointed out as a population especially vulnerable for depression that should not be overlooked in mental health promotion and depression prevention.

Bound on hot-spot mix in high-velocity, high-adiabat direct-drive cryogenic implosions based on comparison of absolute x-ray and neutron yields.

In laser-driven implosions for laboratory fusion, the comparison of hot-spot x-ray yield to neutron production can serve to infer hot-spot mix. For high-performance direct-drive implosions, this ratio depends sensitively on the degree of equilibration between the ion and electron fluids. A scaling for x-ray yield as a function of neutron yield and characteristic ion and electron hot-spot temperatures is developed on the basis of simulations with varying degrees of equilibration. We apply this model to hot-spot x-ray measurements of direct-drive cryogenic implosions typical of the direct-drive designs with best ignition metrics. The comparison of the measured x-ray and neutron yields indicates that hot-spot mix, if present, is below a sensitivity estimated as ∼2% by-atom mix of ablator plastic into the hot spot.

Immune-challenged house wren broods differ in the relative strengths of their responses among different axes of the immune system.

Single components of the immune system are widely used to assess immune function in free-living vertebrates. However, as different immunological components are triggered by different types of threats and may be regulated independently, there is little reason to assume that they should respond similarly if challenged. We investigated whether three commonly assayed immune responses, cutaneous immune activity (phytohaemagglutinin assay), antibody response (tetanus toxoid immunization), and plasma bactericidal activity (Escherichia coli killing) are positively related in nestling house wrens (Troglodytes aedon). Multivariate analysis revealed significant differences in overall immune responsiveness among broods (i.e. nests), primarily attributable to differences in plasma bactericidal activity. Among broods, humoral immune response was negatively related to cutaneous immune activity and positively related to plasma bactericidal activity. We found no significant relationships among these measures of immunity among individual nestlings within broods. Our results suggest that different broods (i.e. families) invest differentially in the various branches of the immune system. Further study is needed to characterize the roles of maternal, genetic and environmental effects on the expression of this physiological bias.

Resolving hot spot microstructure using x-ray penumbral imaging (invited).

We have developed and fielded x-ray penumbral imaging on the National Ignition Facility in order to enable sub-10 µm resolution imaging of stagnated plasma cores (hot spots) of spherically shock compressed spheres and shell implosion targets. By utilizing circular tungsten and tantalum apertures with diameters ranging from 20 µm to 2 mm, in combination with image plate and gated x-ray detectors as well as imaging magnifications ranging from 4 to 64, we have demonstrated high-resolution imaging of hot spot plasmas at x-ray energies above 5 keV. Here we give an overview of the experimental design criteria involved and demonstrate the most relevant influences on the reconstruction of x-ray penumbral images, as well as mitigation strategies of image degrading effects like over-exposed pixels, artifacts, and photon limited source emission. We describe experimental results showing the advantages of x-ray penumbral imaging over conventional Fraunhofer and photon limited pinhole imaging and showcase how internal hot spot microstructures can be resolved.

Biological characterization of purified native 20-kDa human growth hormone.

Because of the propensity of the 20-kDa variant of human growth hormone (GH) to aggregate with itself and with 22-kDa human GH, it has been difficult to prepare monomeric 20-kDa GH in highly purified form. This has been a major complicating factor in determining whether 20-kDa GH has a biological activity profile distinct from that of 22-kDa GH. In the present study, native 20-kDa GH was isolated from a human GH dimer concentrate and purified by a procedure that included column electrophoresis in agarose suspension as a final separation step. This procedure yielded highly purified monomeric 20-kDa GH, which was contaminated to an extent of less than 1% with 22-kDa GH, and which exhibited only a small degree of dimerization upon storage. The native 20-kDa GH was quite active in stimulating growth in hypophysectomized rats, when growth was assessed by body weight gain, longitudinal bone growth, the stimulation of sulfation of cartilage, and the elevation of serum IGF-1 level. However, in all of these growth assays, the 20-kDa GH was somewhat less active than the native 22-kDa GH to which it was compared; e.g., in the body weight gain and longitudinal bone growth assays, it had an estimated potency of 0.6 relative to the 22-kDa GH. The 20-kDa GH exhibited substantial diabetogenic activity when tested for the ability to raise fasting blood glucose concentration and to impair glucose tolerance in ob/ob mice. Also, the native 20-kDa GH had significant in vitro insulin-like activity, although its potency was approximately 20% that of the native 22-kDa GH to which it was compared. Thus, the biological activity profile of native 20-kDa GH differs from that of 22-kDa GH primarily in that insulin-like activity is markedly attenuated.

Alterations in cerebrospinal fluid concentrations of somatostatinlike immunoreactivity in neuropsychiatric disorders.

The concentration of somatostatinlike immunoreactivity in cerebrospinal fluid (CSF) from normal, healthy volunteers (n = 10) and patients with DSM-III diagnoses of major depression (n = 17), schizophrenia (n = 11), or dementia (n = 29) was measured by a sensitive and specific radioimmunoassay. Statistically significant decreases in CSF concentrations of somatostatinlike immunoreactivity were seen in all three patient populations when compared with controls. These findings confirm previous reports of decreased concentrations of somatostatinlike immunoreactivity in the CSF of patients with depression and dementia and extend this observation to patients with schizophrenia as well. These findings are concordant with the view that reductions in somatostatinlike immunoreactivity concentrations are associated with diseases in which cognitive function is disturbed.

Serum haloperidol determinations in psychiatric patients. Comparison of methods and correlation with serum prolactin level.

Twenty-one serum samples from 11 schizophrenic patients receiving long-term haloperidol therapy were analyzed for haloperidol concentrations by two different radioimmunoassays (RIAs) and gas chromatography (GC). There was a good correspondence between the RIA and GC values over a wide range of drug concentrations. However, compared with the specific GC technique, both RIA methods overestimated haloperidol concentrations, reflecting differences in the specificities of the two RIA antibodies. One of the RIA methods had the requisite specificity for application to patients treated with long-term haloperidol therapy, although further methodological refinement will be required for its general clinical application. Haloperidol values determined by GC and RIA analyses correlated highly with prolactin concentrations in the same samples, suggesting that the usefulness of prolactin measurement as an "in vivo bioassay" for circulating levels of haloperidol should be further explored.

The acute effects of growth hormone on amino acid transport and protein synthesis are due to its insulin-like action.

GH has acute stimulatory effects on amino acid transport and protein synthesis in a variety of tissues, but it has not been established whether these effects are expressions of the growth-promoting property of GH or of its separate insulin-like action. The 20,000-dalton structural variant of human GH (20K hGH) has been shown to have a high ratio of growth-promoting to insulin-like activity compared to native hGH (22K hGH), suggesting that it could be used as a tool to address the above question. Therefore, experiments were conducted to compare the relative abilities of native 22K hGH and 20K hGH, when added in vitro, to stimulate amino acid transport and protein synthesis in the isolated diaphragm of the female hypophysectomized rat. Paired intact hemidiaphragms were preincubated for 1 h in the absence or presence of various concentrations of 22K or 20K hGH. Then, 3-O-[14C]methylglucose was added to the medium to measure sugar transport as a test of insulin-like activity, and either alpha-[3H]aminoisobutyric acid acid or [3H] phenylalanine was also added to measure amino acid transport or protein synthesis, respectively, during a final hour of incubation. When the responses to the various concentrations of 22K and 20K were compared, 20K hGH was only about 20% as effective as 22K in stimulating 3-O-methylglucose transport, reflecting its markedly attenuated insulin-like activity on the diaphragm. Similarly, 20K hGH was only 20% as effective as 22K hGH in stimulating alpha-aminoisobutyric acid transport and phenylalanine incorporation into protein in the same muscles. Therefore, these findings support the idea that the rapid stimulatory effects of GH on amino acid transport and protein synthesis are expressions of the insulin-like action of GH and are not components of the response of target cells to its growth-promoting action.

First isolations of Borrelia burgdorferi from rodents collected in northern Europe.

Spirochetes were found in 13% of Ixodes ricinus collected from an island, near Stockholm where human borreliosis is endemic. Borrelia burgdorferi was cultivated from the kidney and/or spleen of wild rodents (Clethrionomys glareolus and Apodemus flavicollis) from the same island. Spirochetes were identified as Borrelia burgdorferi by indirect immunofluorescence assays using species and genus specific monoclonal antibodies. In these tests the spirochetes could not be differentiated from strains previously cultured from Swedish patients with Ixodes-borne borreliosis. The results show that small rodents in Europe may harbour borreliae and indicate that C. glareolus and A. flavicollis may be important reservoirs for the spirochetes causing Ixodes-borne borreliosis in humans and domestic animals in Europe.

Schizophrenia and sex chromosome anomalies.

An apparent excess of sex chromosome aneuploidies (XXY, XXX, and possibly XYY) has been reported in populations of patients with schizophrenia by a number of authors. These reports have received little attention because transmission of psychosis is regarded as autosomal and not sex linked, and the detection of extra X chromosomes by Barr body estimation alone is not a reliable procedure. In this article, we review studies in which either complete karyotypes were determined for the whole sample or in which the presence of a Barr body in an individual was checked by full cytogenetic analysis. We also add two studies (of the former type) of our own--on a Swedish hospital cohort and a United States multiplex-schizophrenia family sample. These data, taken together, suggest that the sex chromosome aneuploidies, XXX and XXY, are increased in population of patients with schizophrenia, whereas too few subjects have been surveyed to determine whether an association also exists with XYY. Nevertheless, we conclude that this is consistent with a gene on the sex chromosomes having influence on the development of schizophrenia. A sex chromosome locus is compatible with an autosomal pattern of transmission if the gene is either pseudoautosomal (i.e., within the exchange region) or X-Y homologous (i.e., present in similar form in the nonrecombining regions of both X and Y chromosomes).

Minimal effective dose and relapse--double-blind trial: haloperidol decanoate vs. placebo.

Fifty-six chronic schizophrenic patients were randomized into haloperidol decanoate (HD) or placebo groups for 48 weeks of double-blind treatment. The double-blind trial was preceded by a 15-week single-blind run-in period, during which all patients were treated with 60 mg of HD (approximately corresponding to 3.6 mg orally/day) every fourth week (except for the second injection, which was given after 3 weeks). Eight relapses occurred during the run-in period, and seven other patients refused further participation. The remaining 41 patients were then treated double blind, either with HD, 60 mg/4 weeks (18 patients), or with placebo (23 patients). Two patients (11%) in the HD group and 16 (69%) in the placebo group relapsed during the 48-week double-blind period. The plasma concentrations of haloperidol were measured every fourth week in both groups. Steady state was reached after 11 weeks. The mean steady-state level was 6.3 nmol/L. In the placebo group, a 50% decrease in the mean haloperidol plasma concentration was seen 8 weeks after withdrawal of haloperidol. The haloperidol plasma concentration was a predictor of relapse. There was no statistical difference between the treatment groups regarding extrapyramidal symptoms. More biperiden, however, was used in the HD group, while the placebo patients took more sedatives. The results of this study show that the relatively low and fixed dose of 60 mg of HD every fourth week was superior to placebo in preventing relapse in schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced regional cerebral blood flow in non-psychotic violent offenders.

The present study was designed to replicate previously reported findings of abnormal frontal and/or temporal cerebral blood flow in violent offenders and to control for the influence of major mental disorder (MMD), substance abuse, and current medication. HMPAO-SPECT-CBF and MRI scans from pretrial forensic psychiatric investigations of 21 subjects convicted of impulsive violent crimes were retrospectively re-evaluated. In 16/21 subjects, visual assessment of SPECT scans showed some hypoperfusion in the temporal and/or frontal lobes. MRI showed no corresponding structural damage. Quantified regional cerebral blood flow (rCBF) in defined regions of interest was compared between index cases and 11 healthy control subjects. Index subjects had significant reductions in the right angular gyrus and the right medial temporal gyrus, bilaterally in the hippocampus, and in the left white frontal matter, but they had significantly increased rCBF in the parietal association cortex bilaterally. The aberrations were as frequent and severe among the subjects without MMD, substance abuse, and current medication (n=7) as in the entire group of index subjects.

Improved soft-agar colony assay in a fluid processing apparatus.

The standard method for quantitating bone marrow precursor cells has been to count the number of colony-forming units that form in semisolid (0.3%) agar. Recently we adapted this assay for use in hardware, the Fluid Processing Apparatus, that is flown in standard payload lockers of the space shuttle. When mouse or rat macrophage colony-forming units were measured with this hardware in ground-based assays, we found significantly more colony growth than that seen in standard plate assays. The improved growth correlates with increased agar thickness but also appears to be due to properties inherent to the Fluid Processing Apparatus. This paper describes an improved method for determining bone marrow macrophage precursor numbers in semisolid agar.

Non-Doppler shift related experimental shock wave measurements using velocity interferometer systems for any reflector.

Velocity interferometer system for any reflectors (VISARs), are becoming increasingly popular in the measurement of shock waves in solids and liquids. VISAR techniques are used in measurements of transit time, speed of shock waves in flight in transparent media [L. C. Chhabildas and J. L. Wise, in Proceedings of the 4th APS Topical Conference on Shock Waves in Condensed Matter, Spokane, Washington, 1985, edited by Y. M. Gupta (Plenum, New York, 1986); P. M. Celliers et al., Appl. Phys. Lett. 73, 1320 (1998)], and in measurements of particle velocity. However, in cases where shock compression or release may change the index of refraction n+ik of the material being studied, the VISAR technique must be applied with care. Changes in n and k introduce phase shifts into the VISAR results that are not associated with changes in velocity. This paper presents a derivation of the theoretical output of a line VISAR that includes the effects of changing n and k and an experimental observation of a non-Doppler shift related effect.

Ritanserin assessments in plasma and CSF by means of HPLC technique with fluorescence detection.

A specific HPLC-technique based on fluorescence detection was developed for assay of ritanserin, a serotonin receptor-blocking agent, in plasma and CSF. In 5 ml sample volumes, the limit of detection was 0.5 ng/ml, the recovery of ritanserin was 83 +/- 5%, and the inter-assay variability, expressed as the coefficient of variation, was 9.5% in the 2-788 ng/ml concentration range. When the values determined by this technique were compared with the results obtained by means of an independent HPLC-method with UV-detection, the coefficient of correlation was 0.995 (p less than 0.001). However, our technique proved to be more specific and less complicated.

HPLC assays of 5-HIAA and tryptophan in cerebrospinal fluid and 5-HT and tryptophan in blood: a methodological study with clinical applications.

HPLC methods were developed for the assay of 5-hydroxy-tryptamine (5-HT) and tryptophan in blood after a simple precipitation step, and 5-hydroxy-indolamine acetic acid (5-HIAA) and tryptophan in CSF by direct injection of CSF. Using these methods, CSF and blood contents were studied in drug-free volunteers and patients treated with tricyclic antidepressant (TCA) drugs. Previously reported variations in the CSF concentrations of 5-HIAA with sex and age were confirmed. No significant difference between patients and healthy subjects were seen in the concentrations of tryptophan in blood or CSF, which were significantly positively intercorrelated. There was no intercorrelation between the concentrations of tryptophan and 5-HIAA in CSF. Highly significant differences between patients and healthy subjects in the platelet-content of 5-HT could be ascribed to the TCA medication. Three TCA drugs, amitriptyline, clomipramine, and imipramine, were compared regarding influence on the platelet-content of 5-HT. Patients treated with clomipramine were found to have considerably lower 5-HT values than imipramine- and amitriptyline-treated patients. A logarithmic model indicated a positive correlation between the two serotonin markers studied, i.e., the amount of platelet-bound 5-HT and the CSF concentrations of 5-HIAA.