Serotonin, Motivation, and Playfulness in the Juvenile Rat

The effects of the selective 5HT1A agonist 8-OH-DPAT were assessed on the play behavior of juvenile rats. When both rats of the test pair were comparably motivated to play, the only significant effect of 8-OH-DPAT was for play to be reduced at higher doses. When there was a baseline asymmetry in playful solicitation due to a differential motivation to play and only one rat of the pair was treated, low doses of 8-OH-DPAT resulted in a collapse of asymmetry in playful solicitations. It did not matter whether the rat that was treated initially accounted for more nape contacts or fewer nape contacts, the net effect of 8-OH-DPAT in this model was for low doses of 8-OH-DPAT to decrease a pre-established asymmetry in play solicitation. It is concluded that selective stimulation of 5HT1A receptors changes the dynamic of a playful interaction between two participants that are differentially motivated to play. These results are discussed within a broader framework of serotonergic involvement in mammalian playfulness

Microfluidic PLGA Microcapsules for the Sustained Delivery of Recombinant Human Bone Morphogenetic Protein 2 in 3D Printed PCL/βTCP Scaffolds

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a clinically available osteoinductive growth factor. In its current form, approved for clinical use, however, the growth factor is delivered in excessively high doses, resulting in unpredictable bone growth and unwanted, sometimes life-threatening, clinical side effects. It has clearly been demonstrated that the sustained, long-term release of the proteins can lead to improved ossification, owing particularly to the rapid metabolism of the biologically active growth factor when delivered alone in solution. Delivery systems for rhBMP-2 have been investigated extensively; yet still, further exploration into the best means of protein delivery — in order to curb the side effect profile and improve the quality of the bone generated — is warranted. The present review of literature introduces extensive work evaluating optimal rhBMP-2 delivery, with particular focus on natural polymers, inorganic materials, as well as synthetic materials. In particular, poly(DL-lactide-co-glycolide) (PLGA) microspheres, conventionally fabricated by a solvent extraction/evaporation procedure, are discussed for their use in sustained drug delivery. The application of rhBMP-2 for bone tissue engineering holds great promise for researchers and clinicians in both the medical and dental fields; yet, there remains a need for further investigation into improved protein delivery mechanisms

The opacity of grains in protoplanetary atmospheres

We have computed the size distribution of silicate grains in the outer radiative region of the envelope of a protoplanet evolving according to the scenario of Pollack et al. (1996). Our computation includes grain growth due to Brownian motion and overtake of smaller grains by larger ones. We also include the input of new grains due to the breakup of planetesimals in the atmosphere. We follow the procedure of Podolak (2003), but have speeded it up significantly. This allows us to test the sensitivity of the code to various parameters. We have also made a more careful estimate of the resulting grain opacity. We find that the grain opacity is of the order of $10^{-2}\ \mathrm{cm^2 g^{-1}}$throughout most of the outer radiative zone as Hubickyj et al. (2005) assumed for their low opacity case, but near the outer edge of the envelope, the opacity can increase to$\sim{1} \mathrm{cm^2 g^{-1}}$. We discuss the effect of this on the evolution of the models.Comment: 28 pages, 13 Figs., to be published in Icarus (accepted Sep. 2007

Sulfur cycling in an iron oxide-dominated, dynamic marine depositional system: The Argentine continental margin

The interplay between sediment deposition patterns, organic matter type and the quantity and quality of reactive mineral phases determines the accumulation, speciation, and isotope composition of pore water and solid phase sulfur constituents in marine sediments. Here, we present the sulfur geochemistry of siliciclastic sediments from two sites along the Argentine continental slope—a system characterized by dynamic deposition and reworking, which result in non-steady state conditions. The two investigated sites have different depositional histories but have in common that reactive iron phases are abundant and that organic matter is refractory—conditions that result in low organoclastic sulfate reduction rates (SRR). Deposition of reworked, isotopically light pyrite and sulfurized organic matter appear to be important contributors to the sulfur inventory, with only minor addition of pyrite from organoclastic sulfate reduction above the sulfate-methane transition (SMT). Pore-water sulfide is limited to a narrow zone at the SMT. The core of that zone is dominated by pyrite accumulation. Iron monosulfide and elemental sulfur accumulate above and below this zone. Iron monosulfide precipitation is driven by the reaction of low amounts of hydrogen sulfide with ferrous iron and is in competition with the oxidation of sulfide by iron (oxyhydr)oxides to form elemental sulfur. The intervals marked by precipitation of intermediate sulfur phases at the margin of the zone with free sulfide are bordered by two distinct peaks in total organic sulfur (TOS). Organic matter sulfurization appears to precede pyrite formation in the iron-dominated margins of the sulfide zone, potentially linked to the presence of polysulfides formed by reaction between dissolved sulfide and elemental sulfur. Thus, SMTs can be hotspots for organic matter sulfurization in sulfide-limited, reactive iron-rich marine sedimentary systems. Furthermore, existence of elemental sulfur and iron monosulfide phases meters below the SMT demonstrates that in sulfide-limited systems metastable sulfur constituents are not readily converted to pyrite but can be buried to deeper sediment depths. Our data show that in non-steady state systems, redox zones do not occur in sequence but can reappear or proceed in inverse sequence throughout the sediment column, causing similar mineral alteration processes to occur at the same time at different sediment depths

The progress of early phase bone healing using porous granules produced from calcium phosphate cement

<p>Abstract</p> <p>Objective</p> <p>Bone grafting is a vital component in many surgical procedures to facilitate the repair of bone defects or fusions. Autologous bone has been the gold standard to date in spite of associated donor-site morbidity and the limited amount of available donor bone. The aim of this study was to investigate the progress of bone regeneration and material degradation of calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder compared to the use of autologous bone grafting in the treatment of "critical size defects" on load-bearing long bones of minipigs.</p> <p>Methods</p> <p>A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft or with micro- and macroporous carbonated, apatic calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. The amount of new bone formation was analysed histomorphometrically.</p> <p>Results</p> <p>The semi-quantitative analysis of the radiological results showed a complete osseous bridging of the defect in three cases for the autograft group. In the same group five animals showed a beginning, but still incomplete bridging of the defect, whereas in the CPG group just two animals developed this. All other animals of the CPG group showed only a still discontinuous new bone formation. Altogether, radiologically a better osseous bridging was observed in the autograft group compared to the CPG group.</p> <p>Histomorphometrical analysis after six weeks of healing revealed that the area of new bone was significantly greater in the autograft group concerning the central area of the defect zone (p < 0.001) as well as the cortical defect zone (p < 0.002). All defects showed new bone formation, but only in the autograft group defects regenerated entirely</p> <p>Conclusions</p> <p>Within the limits of the present study it could be demonstrated that autologous cancellous grafts lead to a significantly better bone regeneration compared to the application of calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder after 6 weeks. In the early phase of bone-healing, the sole application of CPG appears to be inferior to the autologous cancellous grafts in an <it>in vivo </it>critical size defect on load-bearing long bones of mini-pigs.</p

Concomitant Caffeine Increases Binge Consumption of Ethanol in Adolescent and Adult Mice, But Produces Additive Motor Stimulation Only in Adolescent Animals

BACKGROUND: Binge co-consumption of highly caffeinated energy drinks with alcohol (ethanol [EtOH]) has become a common practice among adolescents/young adults and has been associated with an increased incidence of hazardous behaviors. Animal models are critical in advancing our understanding the neurobehavioral consequences of this form of binge drinking. Surprisingly, virtually no work has explored caffeine and EtOH co-consumption or its long-term consequences in adolescent animals. The primary objective of the current study was to extend a previously established mouse model of voluntary binge caffeine and EtOH co-consumption to explore adolescent consumption and responses compared to adults. METHODS: Adolescent and adult male C57BL/6J mice had daily limited access to caffeine (0.03% w/v), EtOH (20% v/v), a combined EtOH/caffeine solution, or water for 14 days via the binge-like drinking paradigm, drinking-in-the-dark (DID). Home cage locomotor activity was measured during DID in a subset of mice. Following DID, all mice rested for 18 days so that adolescents reached adulthood, whereupon all mice underwent 7 days of continuous access 2-bottle choice drinking for 10% (v/v) EtOH or water. RESULTS: Co-consumption with caffeine significantly increased EtOH intake and resultant blood ethanol concentrations in both adolescent and adult mice. In addition, adolescent mice exhibited a uniquely robust locomotor stimulant response to caffeine and EtOH co-consumption. Later EtOH intake and preference was not influenced, however, by prior fluid consumption history via DID. CONCLUSIONS: Together with findings from the human literature, our results suggest that caffeine co-consumption may positively influence binge alcohol consumption in adolescents/young adults. Importantly, this age group may be particularly sensitive to the additive stimulant effects of caffeinated alcohol consumption, an effect which may be related to the high incidence of associated negative outcomes in this population. These observations are particularly concerning considering the heightened plasticity of the adolescent brain

Natural variability of geochemical conditions, biogeochemical processes and element fluxes in sediments of the CCZ

During RV SONNE cruise SO239 in March/April 2015 five sites in the area of the Clarion-Clipperton Fracture Zone (CCZ) in the eastern equatorial Pacific were visited as part of the JPI Oceans pilot action Ecological Aspects of Deep-Sea Mining“. Here, we present a comparable study on (1) the redox zonation in the sediments induced by the input flux of organic matter, (2) biogeochemical reactions including the driver of organic matter degradation and (3) diagenetic manganese redistribution and implications for manganese nodule formation

Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning

Drivers of Iron Cycling in Sediments of the sub-Antarctic Island South Georgia

Sediments of sub-Antarctic islands have been proposed to be important contributors to natural iron fertilization in the Southern Ocean [1, 2]. This potential contribution depends on biogeochemical processes within the sediment that may result in an iron benthic flux, most likely related to the degradation of organic matter (OM). Yet, the OM degradation pathways vary strongly among different sedimentary settings. We elucidate the role of environmental factors on the prevailing biogeochemical pathways and reaction rates at three contrasting sites of South Georgia, using comprehensive solid-phase and pore-water analyses, as well as transportreaction modelling. Samples were obtained along a transect from a glacial fjord towards the shelf during cruise ANTXXIX/ 4 of RV POLARSTERN in 2013. Oxygen penetration depth at all sites is <1 cm. Sediments recovered within the fjord are dominated by dissimilatory iron reduction (DIR) and show very high dissolved Fe2+ concentrations of up to 760 μM, while sulfide was not detected. In addition, Fe reduction below the sulfate/methane transition was observed. High input of reactive iron phases, possibly enhanced by bioturbation and bubble ebullition, appear to favour DIR as the dominant metabolic process for OM degradation in the basin like fjord. Shelf sediments outside the fjord are sulfidic throughout, with H2S formed primarily by anaerobic oxidation of methane. The conversion of Fe oxides into Fe sulfides significantly alters the initial sediment composition along the shelf, and impact the availability of iron to the water column. OM is of marine origin at all three sites (C:N~7), indicating that Fe oxide availability and reactivity rather than the carbon source determine whether iron or sulfate reduction dominantes. [1] Moore & Braucher (2008) Biogeosciences 5, 631-656. [2] Borrione et al., (2014) Biogeosciences 11, 1981–2001