mGluR5 knockout mice exhibit normal conditioned place-preference to cocaine

Metabotropic glutamate receptor 5 (mGluR5) null mutant (-/-) mice have been reported to totally lack the reinforcing or locomotor stimulating effects of cocaine. We tested mGluR5 -/- and +/+ mice for their locomotor and conditioned place- preference response to cocaine. Unlike the previous finding, here we show that compared to mGluR5 +/+ mice, -/- mice exhibit no difference in the locomotor response to low to moderate doses of cocaine (10 or 20 mg/kg). A high dose of cocaine (40 mg/kg) resulted in a blunted rather than absent locomotor response. We tested mGluR5 -/- and +/+ mice for conditioned place-preference to cocaine and found no group differences at a conditioning dose of 10 mg/kg, suggesting normal conditioned rewarding properties of cocaine. These results differ substantially from Chiamulera et al. (2001) and replicates Olsen et al., (2010), who found normal cocaine place-preference in mGluR5 -/- mice at 5 mg/kg. Our results indicate mGluR5 receptors exert a modulatory rather than necessary role in cocaine-induced locomotor stimulation and exert no effect on the conditioned rewarding effects of cocaine

Nucleosynthesis of Heavy Elements by Neutron Capture

Nucleosynthesis of elements heavier than the iron group by neutron capture on both slow and fast time scales is evaluated. The s-process calculations of Clayton, Fowler, Hull, and Zimmerman (1961) have been revised to include more recent experimental results on abundances and neutron capture cross- sections. The solar-system s-process abundances indicate a history of neutron exposure distributions characterized by decreasing probability of high integrated flux; an exponential exposure distribution is extracted. Estimates are made of the s-process contribution to each isotopic abundance; a table gives the amounts of elements produced by each process in the solar-system material. The r-process calculations are carried out using a semi-empirical atomic-mass law to determine neutron-binding energies and betadecay probabilities. The solar-system r-process material has probably been synthesized in two distinct types of environments, e.g., one of about 4 sec duration with temperature 2.4 X 10 K and neutron density 5 X tO , and the other of the same or longer duration with temperature 1.0 X 10 K and neutron density 3 X 1O both of these environments could be found in an object with mass 10 Mo

Nucleosynthesis During Silicon Burning

Silicon burning at temperatures in the neighborhood of 4 × 109 °K has been studied with the aid of a quasiequilibrium model which describes the abundance of the nuclei in the interval 28\u3c~A\u3c~62. It is found that, for a broad range of temperatures and densities, silicon burning leads to nuclear abundance distributions which match important features of the natural solar-system abundance distributions and that a large nuclear energy release accompanies silicon burning

Weak s-Process Irradiations

We calculate the overabundances of rare neutron-rich species produced when seed nuclei between silicon and nickel are exposed to small neutron irradiations in order to ascertain whether those species may owe their natural abundances to such a cause, Particular attention is given to 54Cr and 58Fe, two relatively prominent neutron-rich species that have been bypassed by calculation of explosive nucleosynthesis. Although it is possible that 58Fe is due to weak s-processes, it seems unlikely that 54Cr can be produced along with it because its calculated overabundance is so much less than that of 55Fe. Uncertainties in key neutron-capture cross-sections do not allow this statement to be made unequivocally, however. If 58Fe is due to weak s-process irradiations, moreover, it seems that certain lighter species syn thesixed satisfactorily in explosive oxygen and silicon burning, such as Cl and 41K, must also be synthesixed in the s-process. e regard this as unlikely and therefore doubt that the s-process has played a major role in the synthesis of these nuclei. Accordingly, the origins of 54Cr and 58Fe remain somewhat of a mystery. The suggestion of Amiet and Zek that the rtrocess nuclei are the heavy seeds for the s-process is ruled out

An evolutionary and developmental perspective on the loss of regionalization in the limbs of derived ichthyosaurs

Ichthyosaurs, a lineage of extinct Mesozoic marine reptiles, have garnered attention in both the palaeontological and developmental literature for the unique limb morphology seen in derived genera. These morphologies include an increase in the number of phalanges per digit (hyperphalangy) and in the number of digits (hyperdactyly), but most interestingly also a shift in element identity. Elements distal to the stylopodium acquire characteristics of mesopodial elements, such as a rounded, nodular shape and a loss of perichondral bone on the anterior and posterior surfaces. Here, we examine numerous aspects of the loss of proximodistal identity in ichthyosaur limbs including phylogenetic progression of the loss of perichondral bone, histology and microstructure of the elements retaining perichondral bone in derived taxa, and correlates of intraspecific variation in degree of perichondral bone reduction in a derived ichthyosaur, Stenopterygius quadriscissus. Results show that loss of limb element identity occurred progressively over ichthyosaurian evolution, and the notches seen on the anterior surface of limb elements in derived ichthyosaurs are homologous to the long bone shafts in terrestrial tetrapods. Variation in the number of notches in S. quadriscissus can best be explained through delayed ossification of the anterior perichondrium, indicating a heterochronic component to the loss of identity. We propose a developmental mechanism - gradual expansion of the polyalanine region of HoxD13 over ichthyosaurian evolution - to explain the progressive loss of limb regionalization as well as the heterochronic delay in perichondral ossificatio

Nutritional Modulation of the Proliferation and Activation of Blood Lymphocyte Subsets from Milk Replacer-Fed Calves

Feeding greater quantities of protein and energy to neonatal calves was associated with a reduction in proliferative responses of T lymphocyte subsets to in vitro polyclonal stimulation. Feeding an intensified diet was also associated with altered in vitro expression of activation molecules, CD25, CD44, and CD62L. These data suggest that plane of nutrition during the neonatal period influences lymphocyte-activities essential for the development of a normal immune response

Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis

Background Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis. Methods Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored. Results Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury. Conclusions Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury

Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia

Oligodendrocytes are critical for the development of the plasma membrane and cytoskeleton of the axon. In this paper, we show that fast axonal transport is also dependent on the oligodendrocyte. Using a mouse model of hereditary spastic paraplegia type 2 due to a null mutation of the myelin Plp gene, we find a progressive impairment in fast retrograde and anterograde transport. Increased levels of retrograde motor protein subunits are associated with accumulation of membranous organelles distal to nodal complexes. Using cell transplantation, we show categorically that the axonal phenotype is related to the presence of the overlying Plp null myelin. Our data demonstrate a novel role for oligodendrocytes in the local regulation of axonal function and have implications for the axonal loss associated with secondary progressive multiple sclerosis