Amyloid β Peptides, Signalling and Trafficking of the α7 Nicotine Receptor

The α7 nicotinic acetylcholine receptor (nAChR) is an ionotropic receptor for the neurotransmitter acetylcholine and its precursor, choline. Interestingly, α7 nAChR binds amyloid β 42 (Aβ42) peptide, which has a primary role in Alzheimer’s disease pathology. Aβ42 peptide forms aggregates and different structural forms elicit different physiological outcomes. Oligomeric, fibrillar and non-aggregated preparations of Aβ42 were characterized by atomic force microscopy. Immunoblotting of neuronal cells exposed to these preparations determined oligomeric aggregates of Aβ42 mediate ERK1/2 intracellular signalling through α7 nAChR. Cell surface ionotropic receptors are regulated through endocytosis to maintain the integrity of neurotransmission. Cellular pathways for endocytosis of α7 nAChR are not fully elucidated. Immunocytochemistry, fluorochrome-labelled proteins, and laser-scanning confocal microscopy identified a clathrin-independent flotillin 1- or caveolin 1α-associated pathway for α7 nAChR endocytosis. These studies identify a biologically important form of Aβ42 relevant to α7 nAChR intracellular signalling and an endocytosis pathway for subcellular regulation of α7 nAChR

Kingdom Come

A secret service agent returns home to reconcile with his wife just as the Rapture begins. His scramble to reunite with her becomes all the more urgent when a violent cult begins terrorizing the city in its final hour

New Distribution Records of Ground Beetles From the North Central United States (Coleoptera: Carabidae)

We report 39 ground beetles new to five states in the upper midwestern United States. These species records include 19 new to Illinois (all but one from Lake County), 11 from Iowa, three from South Dakota, eight from Wisconsin, and two from Michigan. (Three species are new to more than one state). Enigmatically disjunct collections include the myrmecophile, Helluomorphoides nigripennis from western Illinois, known previously only from the Atlantic and Gulf coastal plain and piedmont, and Chlaenius amoenus, reported only from southeastern states and now from northeast Iowa

Flares in the Crab Nebula Driven by Untwisting Magnetic Fields

The recent discovery of PeV electrons from the Crab nebula, produced on rapid time scales of one day or less with a sharply peaked gamma-ray spectrum without hard X-rays, challenges traditional models of diffusive shock acceleration followed by synchrotron radiation. Here we outline an accleration model involving a DC electric field parallel to the magnetic field in a twisted toroidal field around the pulsar. Sudden developments of resistivity in localized regions of the twisted field are thought to drive the particle acceleration, up to PeV energies, resulting in flares. This model can reproduce the observed time scales of $T \approx 1$ day, the peak photon energies of $U_{\Phi,rr} \approx 1$ MeV, maximum electron energies of $U_{e,rr} \approx 1$ PeV, and luminosities of $L \approx 10^{36}$ erg s$^{-1}$.Comment: Astrophys. J. Letters, (accepted Apr 30, 2012; in press) - 1 figur

Cardiac-directed expression of a catalytically inactive adenylyl cyclase 6 protects the heart from sustained β-adrenergic stimulation.

ObjectivesIncreased expression of adenylyl cyclase type 6 (AC6) has beneficial effects on the heart through cyclic adenosine monophosphate (cAMP)-dependent and cAMP-independent pathways. We previously generated a catalytically inactive mutant of AC6 (AC6mut) that has an attenuated response to β-adrenergic receptor stimulation, and, consequently, exhibits reduced myocardial cAMP generation. In the current study we test the hypothesis that cardiac-directed expression of AC6mut would protect the heart from sustained β-adrenergic receptor stimulation, a condition frequently encountered in patients with heart failure.Methods and resultsAC6mut mice and transgene negative siblings received osmotic mini-pumps to provide continuous isoproterenol infusion for seven days. Isoproterenol infusion caused deleterious effects that were attenuated by cardiac-directed AC6mut expression. Both groups showed reduced left ventricular (LV) ejection fraction, but the reduction was less in AC6mut mice (p = 0.047). In addition, AC6mut mice showed superior left ventricular function, manifested by higher values for LV peak +dP/dt (p = 0.03), LV peak -dP/dt (p = 0.008), end-systolic pressure-volume relationship (p = 0.003) and cardiac output (p<0.03). LV samples of AC6mut mice had more sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) protein (p<0.01), which likely contributed to better LV function. AC6mut mice had lower rates of cardiac myocyte apoptosis (p = 0.016), reduced caspase 3/7 activity (p = 0.012) and increased B-cell lymphoma 2 (Bcl2) expression (p = 0.0001).ConclusionMice with cardiac-directed AC6mut expression weathered the deleterious effects of continuous isoproterenol infusion better than control mice, indicating cardiac protection

Measurement of isotopically-exchangeable Zn in Zn-deficient paddy soil

The changes in soil chemistry following submergence of a soil for rice production result in zinc (Zn) being immobilized in very insoluble forms. Consequently, Zn deficiency is widespread in rice crops and in human populations that subsist on rice. We explored the use of stable isotopic dilution assays for assessing Zn dynamics in submerged paddy soil with two types of strongly Zn-deficient soil for rice cultivation in the Philippines. We optimized the isotope enrichment, electrolyte and equilibration time to measure isotopically-exchangeable Zn (E-values) without changing redox conditions. Available Zn was rapidly and strongly immobilized following submergence, which was controlled by CO2 accumulation. Addition of the isotopic tracer before submergence produced unreliable E-values because irreversible immobilization of the tracer progressed faster than isotopic exchange. Addition of the tracer to already reduced soil produced stable E-values for tracer–soil contact of up to 1 week. Longer periods produced unreliable E-values because of continuing irreversible fixation of the tracer. We discuss the implications for applications of isotopic dilution methods to measure trace-element dynamics in submerged soil

The effects of sooting in droplet combustion

The study of the burning of a single droplet is an ideal problem from which to gain fundamental understanding of diffusion flame characteristics. Droplet combustion is a complex physico-chemical process that involves a chemically-reacting two-phase flow with phase changes and yet simple experiments and analysis can be used to attain important insights into the burning rate, flame dynamics, kinetic extinction and disruption processes. It is a subject that has been actively studied for the past 40 years with most of the fundamental experiments being performed under reduced-gravity conditions for direct comparisons with theoretical/computational analyses that invoke spherical symmetry assumptions. In the earlier studies, the effects of sooting on the overall burning characteristics were not considered. However, recent microgravity investigations performed at the NASA-LeRC droptowers (Droplet Combustion Experiment) and others indicate that effects of soot and sootcloud formation may be significant during the lifetime of the droplet and therefore must be included in the analysis

Phenotypic Plasticity of Native vs. Invasive Purple Loosestrife: A Two-state Multivariate Approach

The differences in phenotypic plasticity between invasive (North American) and native (German) provenances of the invasive plant Lythrum salicaria (purple loosestrife) were examined using a multivariate reaction norm approach testing two important attributes of reaction norms described by multivariate vectors of phenotypic change: the magnitude and direction of mean trait differences between environments. Data were collected for six life history traits from native and invasive plants using a split-plot design with experimentally manipulated water and nutrient levels. We found significant differences between native and invasive plants in multivariate phenotypic plasticity for comparisons between low and high water treatments within low nutrient levels, between low and high nutrient levels within high water treatments, and for comparisons that included both a water and nutrient level change. The significant genotype × environment (G × E) effects support the argument that invasiveness of purple loosestrife is closely associated with the interaction of high levels of soil nutrient and flooding water regime. Our results indicate that native and invasive plants take different strategies for growth and reproduction; native plants flowered earlier and allocated more to flower production, while invasive plants exhibited an extended period of vegetative growth before flowering to increase height and allocation to clonal reproduction, which may contribute to increased fitness and invasiveness in subsequent years

Symptoms and correlates of anabolic-androgenic steroid dependence

Forty-nine male weight lifters, all users of anabolic-androgenic steroids (AASs), completed an anonymous, self-administered questionnaire to investigate addictive patterns of use. At least one DSM-III-R symptom of dependence was reported by 94% of the sample. Three or more symptoms, consistent with a diagnosis of dependence, were reported by 57%. Dependent users (n=28) could be distinguished from non-dependent users (n=21) by their use of larger doses, more cycles of use, more dissatisfaction with body size, and more aggressive symptoms. Multiple regression analysis revealed that dosage and dissatisfaction with body size were the best predictors of dependent use. Patterns of other substances used, although not predictive of AAS dependence, revealed very low cigarette use and at the same time high alcohol consumption. These data support the notion that AASs are addicting, and suggest that dissatisfaction with body size may lead to dependent patterns of use. The implications for both prevention and treatment are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73678/1/j.1360-0443.1991.tb03101.x.pd

Urocortin 2 Gene Transfer Improves Glycemic Control and Reduces Retinopathy and Mortality in Murine Insulin Deficiency.

Type 1 diabetes affects 20 million patients worldwide. Insulin is the primary and commonly the sole therapy for type 1 diabetes. However, only a minority of patients attain the targeted glucose control and reduced adverse events. We tested urocortin 2 gene transfer as single-agent therapy for insulin deficiency using two mouse models. Urocortin 2 gene transfer reduced blood glucose for months after a single intravenous injection, through increased skeletal muscle insulin sensitivity, increased insulin release in response to glucose stimulation, and increased plasma insulin levels before and during euglycemic clamp. The combined increases in both insulin availability and sensitivity resulted in improved glycemic indices-events that were not anticipated in these insulin-deficient models. In addition, urocortin 2 gene transfer reduced ocular manifestations of long-standing insulin deficiency such as vascular leak and improved retinal function. Finally, mortality was reduced by urocortin 2 gene transfer. The mechanisms for these beneficial effects included increased activities of AMP-activated protein kinase and Akt (protein kinase B) in skeletal muscle, increased skeletal muscle glucose uptake, and increased insulin release. These data suggest that urocortin 2 gene transfer may be a viable therapy for new onset type 1 diabetes and might reduce insulin needs in later stage disease