Dysfunctional Light-Evoked Regulation of cAMP in Photoreceptors and Abnormal Retinal Adaptation in Mice Lacking Dopamine D4 Receptors

Dopamine is a retinal neuromodulator that has been implicated in many aspects of retinal physiology. Photoreceptor cells express dopamine D4 receptors that regulate cAMP metabolism. To assess the effects of dopamine on photoreceptor physiology, we examined the morphology, electrophysiology, and regulation of cAMP metabolism in mice with targeted disruption of the dopamine D4 receptor gene. Photoreceptor morphology and outer segment disc shedding after light onset were normal in D4 knock-out (D4KO) mice. Quinpirole, a dopamine D2/ D3/D4 receptor agonist, decreased cAMP synthesis in retinas of wild-type (WT) mice but not in retinas of D4KO mice. In WT retinas, the photoreceptors of which were functionally isolated by incubation in the presence of exogenous glutamate, light also suppressed cAMP synthesis. Despite the similar inhibition of cAMP synthesis, the effect of light is directly on the photoreceptors and independent of dopamine modulation, because it was unaffected by application of the D4 receptor antagonist L-745,870. Nevertheless, compared with WT retinas, basal cAMP formation was reduced in the photoreceptors of D4KO retinas, and light had no additional inhibitory effect. The results suggest that dopamine, via D4 receptors, normally modulates the cascade that couples light responses to adenylyl cyclase activity in photoreceptor cells, and the absence of this modulation results in dysfunction of the cascade. Dark-adapted electroretinogram (ERG) responses were normal in D4KO mice. However, ERG b-wave responses were greatly suppressed during both light adaptation and early stages of dark adaptation. Thus, the absence of D4 receptors affects adaptation, altering transmission of light responses from photoreceptors to inner retinal neurons. These findings indicate that dopamine D4 receptors normally play a major role in regulating photoreceptor cAMP metabolism and adaptive retinal responses to changing environmental illumination.Fil: Nir, Izhak. The University of Texas Health Science Center; Estados UnidosFil: Harrison, Joseph M.. The University of Texas Health Science Center; Estados UnidosFil: Haque, Rashidul. Emory University School of Medicine; Estados UnidosFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Grandy, David K.. Oregon Health and Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Iuvone, P. Michael. Emory University School of Medicine; Estados Unido

The statistical mechanics of networks

We study the family of network models derived by requiring the expected properties of a graph ensemble to match a given set of measurements of a real-world network, while maximizing the entropy of the ensemble. Models of this type play the same role in the study of networks as is played by the Boltzmann distribution in classical statistical mechanics; they offer the best prediction of network properties subject to the constraints imposed by a given set of observations. We give exact solutions of models within this class that incorporate arbitrary degree distributions and arbitrary but independent edge probabilities. We also discuss some more complex examples with correlated edges that can be solved approximately or exactly by adapting various familiar methods, including mean-field theory, perturbation theory, and saddle-point expansions.Comment: 15 pages, 4 figure

Correlation Functions of Hadron Currents in the QCD Vacuum Calculated in Lattice QCD

Point-to-point vacuum correlation functions for spatially separated hadron currents are calculated in quenched lattice QCD on a $16^3\times 24$ lattice with $6/g^2=5.7$. The lattice data are analyzed in terms of dispersion relations, which enable us to extract physical information from small distances where asymptotic freedom is apparent to large distances where the hadronic resonances dominate. In the pseudoscalar, vector, and axial vector channels where experimental data or phenomenological information are available, semi-quantitative agreement is obtained. In the nucleon and delta channels, where no experimental data exist, our lattice data complement experiments. Comparison with approximations based on sum rules and interacting instantons are made, and technical details of the lattice calculation are described.Comment: 31 pages in REVTeX (with 10 figures to be added using figures command), MIT CTP #214

Quality of Life, Depression, and Healthcare Resource Utilization among Adults with Type 2 Diabetes Mellitus and Concomitant Hypertension and Obesity: A Prospective Survey

Background. This study compared quality of life, depression, and healthcare resource utilization among adults with type 2 diabetes mellitus (T2DM) and comorbid hypertension (HTN) and obesity with those of adults reporting T2DM alone. Methods. Respondents to the US SHIELD survey self-reported their height, weight, comorbid conditions, hospitalizations, and outpatient visits and completed the Short Form-12 (SF-12) and Patient Health Questionnaire (PHQ-9). Respondents reporting T2DM and HTN and obesity (body mass index, BMI, ≥30 kg/m2) were compared with a T2DM-alone group. Results. Respondents with T2DM, HTN, and obesity (n = 1292) had significantly lower SF-12 Physical and Mental Component Summary scores (37.3 and 50.9, resp.) than T2DM-alone respondents (n = 349) (45.8 and 53.5, resp., P < 0.0001). Mean PHQ-9 scores were significantly higher among T2DM respondents with comorbid HTN and obesity (5.0 versus 2.5, P < 0.0001), indicating greater depression burden. Respondents with T2DM, HTN, and obesity had significantly more resource utilization with respect to physician visits and emergency room visits but not hospitalizations than respondents with T2DM alone (P = 0.03). Conclusions. SHIELD respondents with comorbid conditions of T2DM, HTN, and obesity reported greater healthcare resource utilization, more depression symptoms, and lower quality of life than the T2DM-alone group

A Scale-Explicit Framework for Conceptualizing the Environmental Impacts of Agricultural Land Use Changes

Demand for locally-produced food is growing in areas outside traditionally dominant agricultural regions due to concerns over food safety, quality, and sovereignty; rural livelihoods; and environmental integrity. Strategies for meeting this demand rely upon agricultural land use change, in various forms of either intensification or extensification (converting non-agricultural land, including native landforms, to agricultural use). The nature and extent of the impacts of these changes on non-food-provisioning ecosystem services are determined by a complex suite of scale-dependent interactions among farming practices, site-specific characteristics, and the ecosystem services under consideration. Ecosystem modeling strategies which honor such complexity are often impenetrable by non-experts, resulting in a prevalent conceptual gap between ecosystem sciences and the field of sustainable agriculture. Referencing heavily forested New England as an example, we present a conceptual framework designed to synthesize and convey understanding of the scale- and landscape-dependent nature of the relationship between agriculture and various ecosystem services. By accounting for the total impact of multiple disturbances across a landscape while considering the effects of scale, the framework is intended to stimulate and support the collaborative efforts of land managers, scientists, citizen stakeholders, and policy makers as they address the challenges of expanding local agriculture

Trends in Method of Diagnosis of Type 2 Diabetes Mellitus: Results from SHIELD

Aims. This study assessed whether recent screening recommendations have led to increased diagnosis of type 2 diabetes mellitus (T2DM) through routine screening. Methods. Respondents to the 2006 US SHIELD survey reported whether a physician told them they had T2DM, age at diagnosis, specialty of the physician who made the diagnosis, and whether the diagnosis was made after having symptoms, during routine screening, or when being treated for another health problem. Results. Of 3 022 T2DM respondents, 36% of respondents reported that T2DM diagnosis was made during routine screening alone, 20% after having symptoms alone, and 6% when being treated for another health problem alone. The proportion of T2DM respondents reporting a diagnosis based only on screening increased approximately 42% over a 15+-year time span (absolute increase from 31% to 44%) (P < .001), whereas symptom-based diagnosis did not change significantly (P = .10). T2DM was diagnosed primarily by family physicians (88.3%). Conclusion. These findings highlight the importance of regular screening for diabetes and the vital role of primary care physicians in recognizing individuals with T2DM

Lattice Calculation of Point-to-Point Hadron Current Correlation

Point-to-point correlation functions of hadron currents in the QCD vacuum are calculated on a lattice and analyzed using dispersion relations, providing physical information down to small spatial separations. Qualitative agreement with phenomenological results is obtained in channels for which experimental data are available, and these correlation functions are shown to be useful in exploring approximations based on sum rules and interacting instantons.Comment: 11 page

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)

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