Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Noninvasive optical inhibition with a red-shifted microbial rhodopsin

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.McGovern Institute for Brain Research at MIT (Razin Fellowship)United States. Defense Advanced Research Projects Agency. Living Foundries Program (HR0011-12-C-0068)Harvard-MIT Joint Research Grants Program in Basic NeuroscienceHuman Frontier Science Program (Strasbourg, France)Institution of Engineering and Technology (A. F. Harvey Prize)McGovern Institute for Brain Research at MIT. Neurotechnology (MINT) ProgramNew York Stem Cell Foundation (Robertson Investigator Award)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD002002)National Institute of General Medical Sciences (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (Career Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS0848804)Society for Neuroscience (Research Award for Innovation in Neuroscience)Wallace H. Coulter FoundationNational Institutes of Health (U.S.) (RO1 MH091220-01)Whitehall FoundationEsther A. & Joseph Klingenstein Fund, Inc.JPB FoundationPIIF FundingNational Institute of Mental Health (U.S.) (R01-MH102441-01)National Institutes of Health (U.S.) (DP2-OD-017366-01)Massachusetts Institute of Technology. Simons Center for the Social Brai

Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)

This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior

National Outbreak of Acanthamoeba Keratitis Associated with Use of a Contact Lens Solution, United States

Premarket standardized testing for Acanthamoeba spp. is warranted

Ecological release in White Sands lizards

Ecological opportunity is any change that allows populations to escape selection from competition and predation. After encountering ecological opportunity, populations may experience ecological release: enlarged population size, broadened resource use, and/or increased morphological variation. We identified ecological opportunity and tested for ecological release in three lizard colonists of White Sands, New Mexico (Sceloporus undulatus, Holbrookia maculata, and Aspidoscelis inornata). First, we provide evidence for ecological opportunity by demonstrating reduced species richness and abundance of potential competitors and predators at White Sands relative to nearby dark soils habitats. Second, we characterize ecological release at White Sands by demonstrating density compensation in the three White Sands lizard species and expanded resource use in White Sands S. undulatus. Contrary to predictions from ecological release models, we observed directional trait change but not increased trait variation in S. undulatus. Our results suggest that ecological opportunity and ecological release can be identified in natural populations, especially those that have recently colonized isolated ecosystems

Mining a Sea of Data: Deducing the Environmental Controls of Ocean Chlorophyll

Chlorophyll biomass in the surface ocean is regulated by a complex interaction of physiological, oceanographic, and ecological factors and in turn regulates the rates of primary production and export of organic carbon to the deep ocean. Mechanistic models of phytoplankton responses to climate change require the parameterization of many processes of which we have limited knowledge. We develop a statistical approach to estimate the response of remote-sensed ocean chlorophyll to a variety of physical and chemical variables. Irradiance over the mixed layer depth, surface nitrate, sea-surface temperature, and latitude and longitude together can predict 83% of the variation in log chlorophyll in the North Atlantic. Light and nitrate regulate biomass through an empirically determined minimum function explaining nearly 50% of the variation in log chlorophyll by themselves and confirming that either light or macronutrients are often limiting and that much of the variation in chlorophyll concentration is determined by bottom-up mechanisms. Assuming the dynamics of the future ocean are governed by the same processes at work today, we should be able to apply these response functions to future climate change scenarios, with changes in temperature, nutrient distributions, irradiance, and ocean physics

Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)

This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior

Injury rates and injury risk factors among federal bureau of investigation new agent trainees

<p>Abstract</p> <p>Background</p> <p>A one-year prospective examination of injury rates and injury risk factors was conducted in Federal Bureau of Investigation (FBI) new agent training.</p> <p>Methods</p> <p>Injury incidents were obtained from medical records and injury compensation forms. Potential injury risk factors were acquired from a lifestyle questionnaire and existing data at the FBI Academy.</p> <p>Results</p> <p>A total of 426 men and 105 women participated in the project. Thirty-five percent of men and 42% of women experienced one or more injuries during training. The injury incidence rate was 2.5 and 3.2 injuries/1,000 person-days for men and women, respectively (risk ratio (women/men) = 1.3, 95% confidence interval = 0.9-1.7). The activities most commonly associated with injuries (% of total) were defensive tactics training (58%), physical fitness training (20%), physical fitness testing (5%), and firearms training (3%). Among the men, higher injury risk was associated with older age, slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the physical fitness test (PFT), lower self-rated physical activity, lower frequency of aerobic exercise, a prior upper or lower limb injury, and prior foot or knee pain that limited activity. Among the women higher injury risk was associated with slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the PFT, and prior back pain that limited activity.</p> <p>Conclusion</p> <p>The results of this investigation supported those of a previous retrospective investigation emphasizing that lower fitness and self-reported pain limiting activity were associated with higher injury risk among FBI new agents.</p