Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs. Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH.Fil: Thanos, P. K.. NIAAA Intramural Program; Estados Unidos. Brookhaven National Laboratory; Estados Unidos. Universidad de Buenos Aires; ArgentinaFil: Bermeo, C.. Brookhaven National Laboratory; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Suchland, K. L.. Oregon Health & Science University; Estados UnidosFil: Wang, G. J.. Brookhaven National Laboratory; Estados UnidosFil: Grandy, David K.. Oregon Health & Science University; Estados UnidosFil: Volkow, N. D.. NIAAA Intramural Program; Estados Unido

Eleven years of crop diversification alters decomposition dynamics of litter mixtures incubated with soil

Agricultural crop rotations have been shown to increase soil carbon (C), nitrogen (N), and microbial biomass. The mechanisms behind these increases remain unclear, but may be linked to the diversity of crop residue inputs to soil organic matter (SOM). We used a residue mixture incubation to examine how variation in long-term diversity of plant communities in agroecosystems influences decomposition of residue mixtures, thus providing a comparison of the effects of plant diversification on decomposition in the long term (via crop rotation) and short term (via residue mixtures). Three crop residue mixtures, ranging in diversity from two to four species, were incubated for 360 d with soils from five crop rotations, ranging from monoculture corn (mC) to a complex five-crop rotation. In response, we measured fundamental soil pools and processes underlying C and N cycling. These included soil respiration, inorganic N, microbial biomass, and extracellular enzymes. We hypothesized that soils with more diverse cropping histories would show greater synergistic mixture effects than mC. For most variables (except extracellular enzymes), crop rotation history, or the long-term history of plant diversity in the field, had a stronger effect on soil processes than mixture composition. In contrast to our hypothesis, the mC soil had nearly three and seven times greater synergistic mixture effects for respiration and microbial biomass N, respectively, compared with soils from crop rotations. This was due to the low response of the mC soils to poor quality residues (corn and wheat), likely resulting from a lack of available C and nutrients to cometabolize these residues. These results indicate that diversifying crop rotations in agricultural systems alter the decomposition dynamics of new residue inputs, which may be linked to the benefits of increasing crop rotation diversity on soil nutrient cycling, SOM dynamics, and yields

PENGENALAN KONSEP AGROPOLITAN DI KECAMATAN JUMAPOLO KABUPATEN KARANGANYAR

Agropolitan berarti kota yang fokus pada pertanian. Salah satu kawasan yang memiliki potensi pertanian sangat besar adalah Kecamatan Jumapolo yang terletak di Pulau Jawa bagian tengah. Kecamatan ini terletak di daerah subur sehingga sangat cocok untuk budidaya padi. Pemerintah harus memberikan dukungan teknis untuk membantu penduduk desa mempelajari cara terbaik menggunakan sumber daya yang tersedia dan meningkatkan teknik pertanian mereka. Salah satunya dalam penataan peruntukan ruang pertanian agar ke depan dapat menjamin keberlanjutan aktivitas pertanian dan sebagai stategi dalam beradaptasi dalam era globalisasi saat ini dan masa yang akan datang. Penerapan konsep agriculture adalah sebagai suatu konsep permukiman yang melakukan kegiatan yang memanfaatkan hasil pertanian sebagai bahan baku, merancang, dan menyediakan peralatan serta jasa untuk kegiatan tersebut. Pemilihan konsep ini didasari dari karakteristik wilayah deliniasi yang merupakan pertanian. Dengan adanya konsep yang direncanakan di Kecamatan Jumapolo ini, diharapkan dapat membantu dalam mengatasi permasalahan yang ada dan memanfaat potensi yang dimiliki tanpa mengubah karakteristik yang dimiliki wilayah tersebut. Metode yang digunakan adalah metode deskriptif kualitatif. Metode deskripstif kualitatif ini dilakukan apabila peneliti hendak mengeksplor fenomena pada suatu objek yang tidak dapat dikuantifikasikan yang bersifat deskriptif atau naratif. Kata kunci : agropolitan, agriculture, pertania

Microbial activity responses to water stress in agricultural soils from simple and complex crop rotations

Increasing climatic pressures such as drought and flooding challenge agricultural systems and their management globally. How agricultural soils respond to soil water extremes will influence biogeochemical cycles of carbon and nitrogen in these systems. We investigated the response of soils from long-term agricultural field sites under varying crop rotational complexity to either drought or flooding stress. Focusing on these contrasting stressors separately, we investigated soil heterotrophic respiration during single and repeated stress cycles in soils from four different sites along a precipitation gradient (Colorado, MAP 421 mm; South Dakota, MAP 580 mm; Michigan, MAP 893 mm; Maryland, MAP 1192 mm); each site had two crop rotational complexity treatments. At the driest (Colorado) and wettest (Maryland) of these sites, we also analyzed microbial biomass, six potential enzyme activities, and N2O production during and after individual and repeated stress cycles. In general, we found site specific responses to soil water extremes, irrespective of crop rotational complexity and precipitation history. Drought usually caused more severe changes in respiration rates and potential enzyme activities than flooding. All soils returned to control levels for most measured parameters as soon as soils returned to control water levels following drought or flood stress, suggesting that the investigated soils were highly resilient to the applied stresses. The lack of sustained responses following the removal of the stressors may be because they are well in the range of natural in situ soil water fluctuations at the investigated sites. Without the inclusion of plants in our experiment, we found that irrespective of crop rotation complexity, soil and microbial properties in the investigated agricultural soils were more resistant to flooding but highly resilient to drought and flooding during single or repeated stress pulses

Impact of Primary Care–Based Disease Management on the Health-Related Quality of Life in Patients With Type 2 Diabetes and Comorbidity

Contains fulltext : 80343.pdf (publisher's version ) (Closed access)OBJECTIVE: This study examined the effectiveness of the German diabetes disease management program (DMP) for patients with varying numbers of other medical conditions with respect to their health-related quality of life (HRQoL). RESEARCH DESIGN AND METHODS: A questionnaire, including the HRQoL-measured EQ-5D, was mailed to a random sample of 3,546 patients with type 2 diabetes (59.3% female). The EQ-5D score was analyzed by grouping patients according to those on a DMP and those receiving routine care. RESULTS: The analysis showed that participation in the DMP (P < 0.001), the number of other medical conditions (P < 0.001), and the interaction between the DMP and the number of other conditions (P < 0.05) had a significant impact on the EQ-5D score. CONCLUSIONS: Our findings suggest that the number of other medical conditions may have a negative impact on the HRQoL of patients with type 2 diabetes. The results demonstrate that the German DMP for type 2 diabetes may help counterbalance this effect

Long-term pattern and magnitude of soil carbon feedback to the climate system in a warming world

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Science 358 (2017): 101-105, doi:10.1126/science.aan2874.In a 26-year soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon cycling to investigate the potential consequences for the climate system. We found that soil warming results in a four-phase pattern of soil organic matter decay and carbon dioxide fluxes to the atmosphere, with phases of substantial soil carbon loss alternating with phases of no detectable loss. Several factors combine to affect the timing, magnitude, and thermal acclimation of soil carbon loss. These include depletion of microbially accessible carbon pools, reductions in microbial biomass, a shift in microbial carbon use efficiency, and changes in microbial community composition. Our results support projections of a long-term, self-reinforcing carbon feedback from mid-latitude forests to the climate system as the world warms.This research has been supported by grants from the Department of Energy - DE-SC0010740; DOE DE-SC0016590: and the National Science Foundation - DEB 1237491 (LTER) ; DEB 1456528 (LTREB)

Initial soil conditions outweigh management in a cool-season dairy farm\u27s carbon sequestration potential

Pastures and rangelands are a dominant portion of global agricultural land and have the potential to sequester carbon (C) in soils, mitigating climate change. Management intensive grazing (MIG), or high density grazing with rotations through paddocks with long rest periods, has been highlighted as a method of enhancing soil C in pastures by increasing forage production. However, few studies have examined the soil C storage potential of pastures under MIG in the northeastern United States, where the dairy industry comprises a large portion of agricultural use and the regional agricultural economy. Here we present a 12-year study conducted in this region using a combination of field data and the denitrification and decomposition (DNDCv9.5) model to analyze changes in soil C and nitrogen (N) over time, and the climate impacts as they relate to soil carbon dioxide (CO2) and nitrous oxide (N2O) fluxes. Field measurements showed: (1) increases in soil C in grazed fields under MIG (P = 0.03) with no significant increase in hayed fields (P = 0.55); and (2) that the change in soil C was negatively correlated to initial soil C content (P = 0.006). Modeled simulations also showed fields that started with relatively less soil C had significant gains in C over the course of the study, with no significant change in fields with higher initial levels of soil C. Sensitivity analyses showed the physiochemical status of soils (i.e., soil C and clay content) had greater influence over C storage than the intensity of grazing. More extensive grazing methods showed very little change in soil C storage or CO2 and N2O fluxes with modeled continuous grazing trending towards declines in soil C. Our study highlights the importance of considering both initial system conditions as well as management when analyzing the potential for long-term soil C storage

Osiris: A Modern, High-Performance, Coupled, Multi-Physics Code For Nuclear Reactor Core Analysis

To meet the simulation needs of the GNEP program, LLNL is leveraging a suite of high-performance codes to be used in the development of a multi-physics tool for modeling nuclear reactor cores. The Osiris code project, which began last summer, is employing modern computational science techniques in the development of the individual physics modules and the coupling framework. Initial development is focused on coupling thermal-hydraulics and neutral-particle transport, while later phases of the project will add thermal-structural mechanics and isotope depletion. Osiris will be applicable to the design of existing and future reactor systems through the use of first-principles, coupled physics models with fine-scale spatial resolution in three dimensions and fine-scale particle-energy resolution. Our intent is to replace an existing set of legacy, serial codes which require significant approximations and assumptions, with an integrated, coupled code that permits the design of a reactor core using a first-principles physics approach on a wide range of computing platforms, including the world's most powerful parallel computers. A key research activity of this effort deals with the efficient and scalable coupling of physics modules which utilize rather disparate mesh topologies. Our approach allows each code module to use a mesh topology and resolution that is optimal for the physics being solved, and employs a mesh-mapping and data-transfer module to effect the coupling. Additional research is planned in the area of scalable, parallel thermal-hydraulics, high-spatial-accuracy depletion and coupled-physics simulation using Monte Carlo transport

Evidence for the Role of Instantons in Hadron Structure from Lattice QCD

Cooling is used as a filter on a set of gluon fields sampling the Wilson action to selectively remove essentially all fluctuations of the gluon field except for the instantons. The close agreement between quenched lattice QCD results with cooled and uncooled configurations for vacuum correlation functions of hadronic currents and for density-density correlation functions in hadronic bound states provides strong evidence for the dominant role of instantons in determining light hadron structure and quark propagation in the QCD vacuum.Comment: 26 pages in REVTeX, plus 10 figures, uuencoded. Submitted to Physical Review D. MIT-CTP-226

Diffusive limit for a quantum linear Boltzmann dynamics

In this article, I study the diffusive behavior for a quantum test particle interacting with a dilute background gas. The model I begin with is a reduced picture for the test particle dynamics given by a quantum linear Boltzmann equation in which the gas particle scattering is assumed to occur through a hard-sphere interaction. The state of the particle is represented by a density matrix that evolves according to a translation-covariant Lindblad equation. The main result is a proof that the particle's position distribution converges to a Gaussian under diffusive rescaling.Comment: 51 pages. I have restructured Sections 2-4 from the previous version and corrected an error in the proof of Proposition 7.