Variation in stress reactivity affects cage-induced stereotypies in female CD-1 (ICR) mice

Stereotypies in captive animals typically occur under conditions that are stressful for the animals, and there is some anecdotal evidence that stress levels during early stereotypy development predict later stereotypy levels. Based on this and on the involvement of stress in the behavioural sensitization to psychostimulant drugs, it has been hypothesized that stereotypy development might be causally related to stress. To address this question further, we used mice of the commercial outbred stock CD-1 (ICR) and mice of two lines derived from the outbred CD-1 (ICR) strain by selective breeding for high (HR) and low (LR) stress reactivity, respectively, and examined whether genetically driven variation in stress reactivity is associated with variation in the expression of cage-induced stereotypies. From 21 days of age, 10 females of each line were housed in pairs under standard laboratory conditions until they were video recorded for stereotypic behaviour and tested for corticosterone responses in a stress reactivity test (SRT) at 12 weeks of age. As expected, HR females showed a significantly stronger corticosterone response in the SRT than LR females, while ICR females were intermediate. Unexpectedly, however, both HR and LR females showed very low levels of stereotypic behaviour, while ICR females developed the high levels of stereotypies typical for this strain of mouse. Consequently, there was no significant relationship between measures of acute corticosterone reactivity and stereotypy performance, but a trend for reduced recovery of the corticosterone response in the ICR line suggests that variation in recovery rather than the acute response might predict stereotypy levels in these mice. (C) 2011 Elsevier B.V. All rights reserved.

Cage-induced stereotypies in female ICR CD-1 mice do not correlate with recurrent perseveration

Stereotypies are repetitive, unvarying, apparently purposeless behavioural patterns. They develop in animals kept in barren environments and are highly prevalent in laboratory mice (Mus musculus), yet their underlying mechanisms have remained elusive. In humans, stereotypies are associated with several psychiatric disorders and are thought to reflect dysfunction of inhibition of motor programs mediated by the corticostriatal circuitry, resulting in recurrent perseveration (=inappropriate repetition of behavioural responses). Several studies in captive animals of different species have reported a correlation between stereotypy performance and perseverative behaviour, indicating a similar dysfunction. To examine whether stereotypies in mice correlate with recurrent perseveration and whether they are causally related, we raised 40 female ICR CD-1 mice in either barren or enriched cages from three to either six or 16 weeks of age (2 x 2 factorial design) and assessed stereotypic behaviour in the home cage and recurrent perseveration on a two-choice guessing task. Enrichment significantly reduced stereotypic behaviour both at six and 16 weeks of age and recurrent perseveration increased with age. Although enriched housing reduced the number of repetitions in the guessing task significantly, there was no clear evidence for an effect on recurrent perseveration, and recurrent perseveration did not correlate positively with stereotypy level. These findings indicate either that this test did not measure recurrent perseveration or that cage stereotypies in these mice do not reflect behavioural disinhibition as measured by recurrent perseveration.

A Historical-Institutional Study of the Welfare Systems in the United States and Sweden: Net Social Wage Approach

In this study I first look at the historical developments of the welfare systems in Sweden and the United States to understand why these countries have produced two distinct systems over the years. After understanding their historical context I turn to the question of the relationship between the welfare system and economic growth. Policy makers and the mainstream media commonly cite the critique that through government deficit and public debt, welfare systems are a drag on the economy. By calculating the net social wage, the difference in taxes paid and benefits received by workers, I test this hypothesis to see if welfare systems are self-financed by the workers. My findings demonstrate that the net social wage has been negative in the U.S. from 1962 to the early 2000s and in Sweden from 1965 to 2012. This shows that the welfare systems are entirely self-financed by the workers for the full period in Sweden and until the recent financial crisis in the U.S.

Effects of experimental freezing on soil nitrogen dynamics in soils from a net nitrification gradient in a nitrogen-saturated hardwood forest ecosystem

This study examined effects of soil freezing on N dynamics in soil along an N processing gradient within a mixed hardwood dominated watershed at Fernow Experimental Forest, West Virginia. Sites were designated as LN (low rates of N processing), ML (moderately low), MH (moderately high), and HN (high). Soils underwent three 7-day freezing treatments (0, –20, or –80 °C) in the laboratory. Responses varied between temperature treatments and along the gradient. Initial effects differed among freezing treatments for net N mineralization, but not nitrification, in soils across the gradient, generally maintained at LN < ML ≤ MH < HN for all treatments. Net N mineralization potential was higher following freezing at –20 and –80 °C than control; all were higher than at 0 °C. Net nitrification potential exhibited similar patterns. LN was an exception, with net nitrification low regardless of treatment. Freezing response of N mineralization differed greatly from that of nitrification, suggesting that soil freezing may decouple two processes of the soil N cycle that are otherwise tightly linked at our site. Results also suggest that soil freezing at temperatures commonly experienced at this site can further increase net nitrification in soils already exhibiting high nitrification from N saturation.

Effects of in situ freezing on soil net nitrogen mineralization and net nitrification in fertilized grassland of northern China

Effects of soil freezing on nitrogen (N) mineralization have been the subject of increased attention in the ecological literature, though fewer studies have examined N mineralization responses to successive mild freezing, severe freezing and cyclic freeze–thaw events. Even less is known about relationships of responses to soil N status. This study measured soil N mineralization and nitrification in the field along an experimental N gradient in a grassland of northern China during the dormant season (October 2005–April 2006), a period in which freezing naturally occurs. Net N mineralization exhibited great temporal variability, with nitrification being the predominant N transformation process. Soil microbial biomass C and N and extractable NH4 + pools declined by 40, 52, and 56%, respectively, in April 2006, compared with their initial concentrations in October 2005; soil NO3– pools increased by 84%. Temporal patterns of N mineralization were correlated with soil microbial biomass C and N. N mineralization and nitrification increased linearly with added N. Microbial biomass C in treated soils increased by 10% relative to controls, whereas microbial N declined by 9%. Results further suggest that freezing events greatly alter soil N dynamics in the dormant season at this site, with considerable available N accumulating during this period.

Peptide receptor expression in GEP-NET

Numerous peptide receptors have recently been reported to be expressed or overexpressed in various human cancers. For instance, somatostatin receptors are particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors (GEP-NET), including both primaries and metastases. The density is often high, and the distribution is usually homogenous. While various somatostatin receptor subtypes can be expressed in these tumors, the sst(2) is clearly predominant. These receptors represent the molecular basis for a number of clinical applications, including symptomatic therapy with octreotide in hormone-secreting GEP-NET, in vivo diagnostic with radiolabeled diethylene triamine pentaacetic acid octreotide (Octreoscan) to evaluate the extend of the disease, and (90)Y- or (177)Lu-[(90)Y-DOTA]-D: -Phe(1)-Tyr(3) octreotide radiotherapy. GEP-NET can, however, express peptide receptors other than somatostatin receptor: Insulinomas have more glucagon-like peptide 1 receptors than somatostatin receptors; gastrinomas express very high levels of secretin receptors. GEP-NET may also express cholecystokinin 2, bombesin, neuropeptide Y, or vasoactive intestinal peptide receptors. Often, several of these peptide receptors are expressed simultaneously in GEP-NET, providing a molecular basis for in vivo multireceptor targeting of those tumors.

Proteins in silico-modeling and sampling

Proteins are linear chain molecules made out of amino acids. Only when they fold to their native states, they become functional. This dissertation aims to model the solvent (environment) effect and to develop & implement enhanced sampling methods that enable a reliable study of the protein folding problem in silico. We have developed an enhanced solvation model based on the solution to the Poisson-Boltzmann equation in order to describe the solvent effect. Following the quantum mechanical Polarizable Continuum Model (PCM), we decomposed net solvation free energy into three physical terms– Polarization, Dispersion and Cavitation. All the terms were implemented, analyzed and parametrized individually to obtain a high level of accuracy. In order to describe the thermodynamics of proteins, their conformational space needs to be sampled thoroughly. Simulations of proteins are hampered by slow relaxation due to their rugged free-energy landscape, with the barriers between minima being higher than the thermal energy at physiological temperatures. In order to overcome this problem a number of approaches have been proposed of which replica exchange method (REM) is the most popular. In this dissertation we describe a new variant of canonical replica exchange method in the context of molecular dynamic simulation. The advantage of this new method is the easily tunable high acceptance rate for the replica exchange. We call our method Microcanonical Replica Exchange Molecular Dynamic (MREMD). We have described the theoretical frame work, comment on its actual implementation, and its application to Trp-cage mini-protein in implicit solvent. We have been able to correctly predict the folding thermodynamics of this protein using our approach.

Compressive strength of interbody cages in the lumbar spine: the effect of cage shape, posterior instrumentation and bone density

One goal of interbody fusion is to increase the height of the degenerated disc space. Interbody cages in particular have been promoted with the claim that they can maintain the disc space better than other methods. There are many factors that can affect the disc height maintenance, including graft or cage design, the quality of the surrounding bone and the presence of supplementary posterior fixation. The present study is an in vitro biomechanical investigation of the compressive behaviour of three different interbody cage designs in a human cadaveric model. The effect of bone density and posterior instrumentation were assessed. Thirty-six lumbar functional spinal units were instrumented with one of three interbody cages: (1) a porous titanium implant with endplate fit (Stratec), (2) a porous, rectangular carbon-fibre implant (Brantigan) and (3) a porous, cylindrical threaded implant (Ray). Posterior instrumentation (USS) was applied to half of the specimens. All specimens were subjected to axial compression displacement until failure. Correlations between both the failure load and the load at 3 mm displacement with the bone density measurements were observed. Neither the cage design nor the presence of posterior instrumentation had a significant effect on the failure load. The loads at 3 mm were slightly less for the Stratec cage, implying lower axial stiffness, but were not different with posterior instrumentation. The large range of observed failure loads overlaps the potential in vivo compressive loads, implying that failure of the bone-implant interface may occur clinically. Preoperative measurements of bone density may be an effective tool to predict settling around interbody cages.