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.     

Structure of the polycrystalline zeolite catalyst IM-5 solved by enhanced charge flipping

Despite substantial advances in crystal structure determination methodology for polycrystalline materials, some problems have remained intractable. A case in point is the zeolite catalyst IM-5, whose structure has eluded determination for almost 10 years. Here we present a charge-flipping structure-solution algorithm, extended to facilitate the combined use of powder diffraction and electron microscopy data. With this algorithm, we have elucidated the complex structure of IM-5, with 24 topologically distinct silicon atoms and an unusual two-dimensional medium-pore channel system. This powerful approach to structure solution can be applied without modification to any type of polycrystalline material (e.g., catalysts, ceramics, pharmaceuticals, complex metal alloys) and is therefore pertinent to a diverse range of scientific disciplines.     

Shrinking Danish agriculture

Danish agriculture is facing a turning point. Centuries of struggle to increase arable land area as well as its productivity is about to be reversed, due to overproduction and environmental problems. Some land will probably be turned back to nature, and the use of chemicals in agriculture in general will be reduced, perhaps with a lower productivity and a better environment as a consequence. This paper mainly describes some of the political actions taken in Denmark to influence environmental-agricultural issues. First, however, some of the recently perceived environmental problems and over-production problems connected with Danish farming are outlined.     

Characteristics and conflicts in Norwegian agriculture

This article raises the issue of the extent to which a single nation can develop a “national agricultural policy,” pursuing internal goals in agrarian development, goals that vary significantly from those of other industrialized countries. What are the conflicts arising from such a policy and how do these conflicts interfere with the general agricultural crisis of these countries? The Norwegian case is explored as an example of a blend of social-democratic and center-populist agricultural policies. The decision in 1975 by the Norwegian Parliament to establish the income level of farmers at the same level as workers is seen as an experiment. As agricultural policy, this new departure represented a deviation from the earlier policies of rationalization. The Social Democrats developed their new position as a result of internal and external pressure. A series of reforms financed by the new state incomes from oil production were undertaken, of which income equalization and a farm relief service were the most important. Most Norwegian farmers speak of the reform years as “the good years of escalation.” Equity was reached in 1982, but nevertheless several problems emerged: 1) the escalation of subsidized incomes led to overproduction and decreasing incomes from the market (after 1982), 2) the large budgetary transfers to agriculture caused a legitimation crisis, fueling the constituency of the right-wing Progress Party, 3) the large subsidies to agriculture contributed to the fiscal crisis of the state, 4) the problems mentioned above, contributed to the general crisis of the Norwegian Social Democracy which finds itself with dwindling support. The likely outcome of the present Norwegian farm crisis is the implementation of an agricultural policy that will protect the most vulnerable sector and open the more competitive sector to market forces.     

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.     

A slowly progressive retinopathy in the Shetland Sheepdog

Objective To describe a slowly progressive retinopathy (SPR) in Shetland Sheepdogs. Animals Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of SPR and six normal Shetland Sheepdogs were included in the study. Procedure Ophthalmic examination including slit‐lamp biomicroscopy and ophthalmoscopy was performed in all dogs. Electroretinograms and obstacle course‐test were performed in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups according to their dark‐adapted b‐wave amplitudes. SPR1‐dogs had ophthalmoscopic signs of SPR, but normal dark‐adapted b‐wave amplitudes. Dogs with both ophthalmoscopic signs and subnormal, dark‐adapted b‐wave amplitudes were assigned to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination. Results The ophthalmoscopic changes included bilateral, symmetrical, greyish discoloration in the peripheral tapetal fundus with normal or marginally attenuated vessels. Repeated examination showed that the ophthalmoscopic changes slowly spread across the central parts of the tapetal fundus, but did not progress to obvious neuroretinal thinning presenting as tapetal hyper‐reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed significantly reduced b‐wave amplitudes throughout dark‐adaptation. Microscopy showed thinning of the outer nuclear layer and abnormal appearance of rod and cone outer segments. Testing for the progressive rod–cone degeneration ( prcd )‐mutation in three dogs with SPR was negative. Conclusion Slowly progressive retinopathy is a generalized rod–cone degeneration that on ophthalmoscopy looks similar to early stages of progressive retinal atrophy. The ophthalmoscopic findings are slowly progressive without tapetal hyper‐reflectivity. Visual impairment is not obvious and the electroretinogram is more subtly altered than in progressive retinal atrophy. The etiology remains unclear. SPR is not caused by the prcd‐mutation.     

Blood parameters in Swedish dairy herds with high or low incidence of displaced abomasum or ketosis

Sixty dairy herds were studied to investigate the association between long-term incidence of displaced abomasum and clinical ketosis and body condition score and blood profiles, including parameters estimating energy metabolism and hepatic lipidosis in the periparturient period and early lactation. Blood samples were taken around parturition and in early lactation from cows without apparent clinical symptoms of metabolic disorders. A difference in metabolism between high and low incidence herds was shown post-partum by a lower metabolic index (the revised Quantitative Insulin Sensitivity Check Index, RQUICKI), and tendencies for higher concentrations of glucose, insulin and non-esterified fatty acids in the high incidence herds. High incidence herds had more cows and produced on average 1400kg energy-corrected milk per cow per year more than the low incidence herds. No differences were found in parameters reflecting liver cell damage. In the first 3weeks post-partum the RQUICKI was a more sensitive marker of herds with a high incidence of displaced abomasum and clinical ketosis than any of the individual parameters, but further research is needed before practical applications of the RQUICKI can be foreseen.