<Emphasis Type="Italic">parkin</Emphasis> counteracts symptoms in a <Emphasis Type="Italic">Drosophila</Emphasis> model of Parkinson's disease

Background

Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α-synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α-synuclein in Drosophila neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD.

Results

To investigate the role of parkin, we have generated transgenic Drosophila that conditionally express parkin under the control of the yeast UAS enhancer. While expression of parkin has little consequence, co-expression of parkin with α-synuclein in the dopaminergic neurons suppresses the α-synuclein-induced premature loss of climbing ability. In addition directed expression of parkin in the eye counteracts the α-synuclein-induced degeneration of the ommatidial array. These results show that parkin suppresses the PD-like symptoms observed in the α-synuclein-dependent Drosophila model of PD.

Conclusion

The highly conserved parkin E3 ubiquitin ligase can suppress the damaging effects of human α-synuclein. These results are consistent with a role for parkin in targeting α-synuclein to the proteasome. If this relationship is conserved in humans, this suggests that up-regulation of parkin should suppress α-synucleinopathic PD. The development of therapies that regulate parkin activity may be crucial in the treatment of PD.

     

Liquid-crystalline phase behavior of a colloidal rod-plate mixture

The phase behavior of rod-plate mixtures was investigated using model systems containing unambiguously rod- and plate-shaped colloids. We find that the theoretically disputed biaxial nematic phase is unstable with respect to demixing into an isotropic and two uniaxial nematic phases. The phase behavior at very high densities is exceptionally rich and includes the coexistence of up to four different liquid crystalline phases, which stem from the coupling between the employed particle shapes and polydispersity.     

DEKOIS: demanding evaluation kits for objective in silico screening--a versatile tool for benchmarking docking programs and scoring functions

For widely applied in silico screening techniques success depends on the rational selection of an appropriate method. We herein present a fast, versatile, and robust method to construct demanding evaluation kits for objective in silico screening (DEKOIS). This automated process enables creating tailor-made decoy sets for any given sets of bioactives. It facilitates a target-dependent validation of docking algorithms and scoring functions helping to save time and resources. We have developed metrics for assessing and improving decoy set quality and employ them to investigate how decoy embedding affects docking. We demonstrate that screening performance is target-dependent and can be impaired by latent actives in the decoy set (LADS) or enhanced by poor decoy embedding. The presented method allows extending and complementing the collection of publicly available high quality decoy sets toward new target space. All present and future DEKOIS data sets will be made accessible at www.dekois.com.     

Cross-sections for deuteron photo-disintegration from 139 to 832 MeV

The cross-sections for deuteron photo-disintegration have been measured at nine c.m. angles from 37 to 143 degrees. The minimum and maximum photon energies have been 139 and 832 MeV respectively. The results are in agreement with earlier data above 300 MeV, but are significantly larger below 200 MeV, the discrepancies being up to 50% at the lowest energies measured.     

Helicobacter pylori determination in non-municipal drinking water and epidemiological findings

Background.?Studies conducted in Europe as well as in North and South America have tried to link Helicobacter pylori colonization with the drinking water supply, especially since H. pylori is known to survive quite well in water.

Methods.?In 2000, a cohort of 1884 grade-two children from two rural counties surrounding the city of Leipzig, Germany (77.4% of the 1991/1992 birth cohort) were tested for H. pylori colonization using the [¹³C]urea breath test. A parent-completed questionnaire elicited details on living conditions and lifestyle habits including questions on the children's drinking water from sources other than public water supplies, swimming in natural waters, etc.

In a second independent study, samples of well water, taken from 157 private wells still used in the two counties, were being tested for the presence of H. pylori, using polymerase chain reaction (PCR) method to determine relevant target DNA fragments of H. pylori.

Results.?In county I, 5.7% of the children and in county II 6.6% tested H. pylori-positive. Cluster analyses of the questionnaire data in both counties pointed to ‘drinking water from other than municipal sources’, as the closest H. pylori-associated cluster variable. The cluster estimations were supported by odds ratio (OR) calculations with an OR?=?16.4 (95% confidence interval (CI) 3.1,…,88.5) for county I and OR?=?4.0 (95% CI 1.3,…,12.4) for county II.

The PCR analyses showed H. pylori DNA fragments in 10.8% of the wells in county I and 9.2% in county II. The detection limit was set at 10 DNA copies corresponding to 125?bacteria/L, the average infestation of these wells was 931?bacteria/L.

Conclusion.?Despite the fact that the microbiological and epidemiological data do not correspond except that both studies were conducted in the same geographical areas, the independent findings of H. pylori in well water in the same general areas where children do seem to drink water other than from the public water supply suggests that water may be an important source of H. pylori infection.     

Role of the critical micelle concentration in the electrochemical deposition of nanostructured ZnO films under utilization of amphiphilic molecules

A detailed understanding of micelle formation that occurs above a critical micelle concentration (cmc) is a crucial point for the surfactant-assisted preparation of porous materials such as molecular sieves. However, the role of the cmc in the surfactant-assisted electrodeposition of porous oxides is widely unknown. In this study, we investigated the electrodeposition of ZnO films under utilization of alkyl sulfates and alkyl sulfonates with different chain lengths. Cmc values of the surfactants were measured directly in the electrodeposition bath by surface tension measurements. Subsequently, we performed electrodeposition with surfactant concentrations from above the cmc down to concentrations well below the cmc. Beside a lamellar ZnO phase already known from earlier studies, a second nanoparticular ZnO phase was found at concentrations below the cmc.     

Substituent Effects on Hydrogen Bonding in Watson–Crick Base Pairs. A Theoretical Study

We have theoretically analyzed Watson–Crick AT and GC base pairs in which purine C8 and/or pyrimidine C6 positions carry a substituent X = H, F, Cl or Br, using the generalized gradient approximation (GGA) of density functional theory at BP86/TZ2P. The purpose is to study the effects on structure and hydrogen bond strength if X = H is substituted by a halogen atom. Furthermore, we wish to explore the relative importance of electrostatic attraction versus orbital interaction in the above multiply hydrogen-bonded systems, using a quantitative bond energy decomposition scheme. We find that replacing X = H by a halogen atom has relatively small yet characteristic effects on hydrogen bond lengths, strengths and bonding mechanism. In general, it reduces the hydrogen-bond-accepting- and increases the hydrogen-bond-donating capabilities of a DNA base. The orbital interaction component in these hydrogen bonds is found for all substituents (X = H, F, Cl, and Br) to contribute about 41% of the attractive interactions and is thus of the same order of magnitude as the electrostatic component, which provides the remaining 59% of the attraction.