Role of brain insulin receptor in control of body weight and reproduction

Insulin receptors (IRs) and insulin signaling proteins are widely distributed throughout the central nervous system (CNS). To study the physiological role of insulin signaling in the brain, we created mice with a neuron-specific disruption of the IR gene (NIRKO mice). Inactivation of the IR had no impact on brain development or neuronal survival. However, female NIRKO mice showed increased food intake, and both male and female mice developed diet-sensitive obesity with increases in body fat and plasma leptin levels, mild insulin resistance, elevated plasma insulin levels, and hypertriglyceridemia. NIRKO mice also exhibited impaired spermatogenesis and ovarian follicle maturation because of hypothalamic dysregulation of luteinizing hormone. Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction.     

Molecular and neuronal substrate for the selective attenuation of anxiety

Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the alpha2 or alpha3 GABAA (gamma-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the alpha2(H101R) point mutation but present in mice with the alpha3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by alpha2 GABAA receptors, which are largely expressed in the limbic system, but not by alpha3 GABAA receptors, which predominate in the reticular activating system.     

Quantum spin hall insulator state in HgTe quantum wells

Recent theory predicted that the quantum spin Hall effect, a fundamentally new quantum state of matter that exists at zero external magnetic field, may be realized in HgTe/(Hg,Cd)Te quantum wells. We fabricated such sample structures with low density and high mobility in which we could tune, through an external gate voltage, the carrier conduction from n-type to p-type, passing through an insulating regime. For thin quantum wells with well width d < 6.3 nanometers, the insulating regime showed the conventional behavior of vanishingly small conductance at low temperature. However, for thicker quantum wells (d > 6.3 nanometers), the nominally insulating regime showed a plateau of residual conductance close to 2e(2)/h, where e is the electron charge and h is Planck's constant. The residual conductance was independent of the sample width, indicating that it is caused by edge states. Furthermore, the residual conductance was destroyed by a small external magnetic field. The quantum phase transition at the critical thickness, d = 6.3 nanometers, was also independently determined from the magnetic field-induced insulator-to-metal transition. These observations provide experimental evidence of the quantum spin Hall effect.     

Diagnostic accuracy of PCR for Jaagsiekte sheep retrovirus using field data from 125 Scottish sheep flocks

Using a representative sample of Scottish sheep comprising 125 flocks, the sensitivity and specificity of PCR for Jaagsiekte sheep retrovirus (JSRV) was estimated. By combining and adapting existing methods, the characteristics of the diagnostic test were estimated (in the absence of a gold standard reference) using repeated laboratory replicates. As the results of replicates within the same animal cannot be considered to be independent, the performance of the PCR was calculated at individual replicate level.The median diagnostic specificity of the PCR when applied to individual animals drawn from the Scottish flock was estimated to be 0.997 (95% confidence interval [CI] 0.996–0.999), whereas the median sensitivity was 0.107 (95% CI 0.077–0.152). Considering the diagnostic test as three replicates where a positive result on any one or more replicates results in a positive test, the median sensitivity increased to 0.279. Reasons for the low observed sensitivity were explored by comparing the performance of the test as a function of the concentration of target DNA using spiked positive controls with known concentrations of target DNA. The median sensitivity of the test when used with positive samples with a mean concentration of 1.0 target DNA sequence per 25 μL was estimated to be 0.160, which suggests that the PCR had a high true (analytical) sensitivity and that the low observed (diagnostic) sensitivity in individual samples was due to low concentrations of target DNA in the blood of clinically healthy animals.     

Use of the O Horizon of Forest Soils in Monitoring Metal Deposition in Latvia

The concentrations of Cu, Cd, Pb, Zn, V,Ni, Cr, Fe Ca, Mg and K were determined in the organicsoil layer (O horizon) of pine forests in Latvia. Theconcentrations were expressed on a mass, volume andsurface area basis. When concentrations were calculatedper unit mass of the O horizon, significant positivecorrelations between concentrations in the O horizon andPleurozium schreberi were achieved for mostelements (excepting Cr, Ca and K), and to lesser degreesfor Cu, Pb, Zn, V, Ni and Fe when calculated on a volumeor area basis. Non-rotated principal components analysisidentified a major soil factor related to bulk density(volume- and area-based concentrations). The main groupsof related elements defined by varimax-rotated PCAcomponents were similar for the mass- and volume-baseddata, and regions with elevated levels of these elementscould be related to local pollution sources, similar tothe patterns previously reported from surveys based onmoss.     

Mass spectrometric detection and formation of D-amino acids in processed plant saps, syrups, and fruit juice concentrates

Liquid and syrupy dietary saps and juices of plant origin, characterized by the presence of large quantities of saccharides (glucose, fructose, or sucrose) and containing amino acids, were analyzed for the presence of D-amino acids using enantioselective gas chromatography-mass spectrometry. D-amino acids were detected in processed saps and juices of trees (maple, palm, birch), fruits (grape, apple, pear, pomegranate, date), and various other plants (agave, beetroot, sugar cane, carob). D-Ala was detected in all plant products and amounted to approximately 34% D-Ala (relative to L-Ala + D-Ala) in Canadian maple syrups, to approximately 13% in palm saps, and to 48 and 13% D-Ala, respectively, in concentrated grape juices (Spanish Arrope and Turkish Pekmez). Varying amounts and kinds of other D-amino acids were also detected. To test the hypothesis that racemization, that is, partial conversion of L-amino acids into their corresponding D-enantiomers, occurs at reversible stages of the Maillard reaction, the Amadori compound fructose-L-phenylalanine was synthesized. On heating at 200 degrees C for 5 (20) min, release of 10.8% (24.2%) D-Phe was detected. From the data it is concluded that the Amadori compounds formed in the course of the Maillard reaction are pecursors of D-amino acids in foodstuffs.     

The synergism of Actinobacillus pleuropneumoniae and influenza A virus in experimentally-infected mice

Models for infecting mice with Influenza A-Virus (A/PR 8/34, H0N1) and Actinobacillus pleuropneumoniae (serotype 9) were developed in Han: NMRI-mice. After infecting mice with sublethal doses of one of the infectious agents, or both together as a mixed infection, animals were subsequently exsanguinated and the lungs washed by bronchoalveolar lavage. Clinical symptoms were recorded daily, examination of lung lavage fluid and sera as well as histology of the lungs were done. An increase in mortality, weight reduction and total cell yield of lung lavage fluid was observed after mixed infection. Compared to mixed infections total protein content and elastase in sera and lung lavage fluid after singular ones were raised not as much. In lung lavage fluid the total cell yield was increased more marked. These alterations indicate a synergistic effect of viruses and bacteria, developed by mixed infection as well as a bacterial infection on top of a viral one. Histopathologically the lung alterations were found to depend on the infectious agent and the mode of infection.