Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta

DNA polymerase eta (Pol eta) is a eukaryotic lesion bypass polymerase that helps organisms to survive exposure to ultraviolet (UV) radiation, and tumor cells to gain resistance against cisplatin-based chemotherapy. It allows cells to replicate across cross-link lesions such as 1,2-d(GpG) cisplatin adducts (Pt-GG) and UV-induced cis-syn thymine dimers. We present structural and biochemical analysis of how Pol eta copies Pt-GG-containing DNA. The damaged DNA is bound in an open DNA binding rim. Nucleotidyl transfer requires the DNA to rotate into an active conformation, driven by hydrogen bonding of the templating base to the dNTP. For the 3'dG of the Pt-GG, this step is accomplished by a Watson-Crick base pair to dCTP and is biochemically efficient and accurate. In contrast, bypass of the 5'dG of the Pt-GG is less efficient and promiscuous for dCTP and dATP as a result of the presence of the rigid Pt cross-link. Our analysis reveals the set of structural features that enable Pol eta to replicate across strongly distorting DNA lesions.     

Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1

The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioral adaptation to stress and is causally linked to emotional disorders. Using neurochemical and genetic tools, we determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid-containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders.     

Complex multicolor tilings and critical phenomena in tetraphilic liquid crystals

T-shaped molecules with a rod-like aromatic core and a flexible side chain form liquid crystal honeycombs with aromatic cell walls and a cell interior filled with the side chains. Here, we show how the addition of a second chain, incompatible with the first (X-shaped molecules), can form honeycombs with highly complex tiling patterns, with cells of up to five different compositions ("colors") and polygonal shapes. The complexity is caused by the inability of the side chains to separate cleanly because of geometric frustration. Furthermore, a thermoreversible transition was observed between a multicolor (phase-separated) and a single-color (mixed) honeycomb phase. This is analogous to the Curie transition in simple and frustrated ferro- and antiferromagnets; here spin flips are replaced by 180° reorientations of the molecules.     

Conservation policies and planning under climate change

Biodiversity conservation policies focus on securing the survival of species and habitats according to their current distribution. This basic premise may be inappropriate for halting biodiversity decline under the dynamic changes caused by climate change. This study explores a dynamic spatial conservation prioritization problem where climate change gradually changes the future habitat suitability of a site’ current species. This has implications for survival probability, as well as for species that potentially immigrate to the site. The problem is explored using a set of heuristics for both of two policy objectives focusing on (1) the protection on current (native) species, and (2) all species, including immigrating species. The trade-offs between the protection of native species versus all species is illustrated. The study shows that the development of prediction models of future species distributions as the basis of decision rules can be crucial for ensuring the effectiveness of conservation plans. Finally, it is discussed how more adaptive strategies, that allow for the redirection of resources from protected sites to privately-owned sites, may increase the effectiveness of the conservation networks. Climate change induced shifts in the suitability of habitats for species may increase the value of such adaptive strategies, the benefit decreasing with increasing migration probabilities and species distribution dynamics.     

Pedo‐ecological consequences of lithological discontinuities in soils—examples from Central Europe

Soil profiles having lithological discontinuities, i.e., stratified or layered profiles, occur worldwide. Their genesis as part of the upper‐regolith formation is comparatively well understood, particularly in Central Europe where extensive research on relic periglacial cover beds has been done. But the pedogenetic and ecological implications of lithologically discontinuous soils (LDS) are less well known. Most textbooks rely on the so‐called A‐B‐C‐model as a climate‐driven approach to soil formation. After reviewing definitions and concepts of lithological discontinuities and how they form, we present a pedogenetic model extending the traditional approach by considering substrate genesis and regolith dynamics. The consequences in the interpretation of vertical distributions of parameters of soil acidification and of heavy metals are investigated for typical soil profiles from the W Ore Mountains and the central‐German lowlands. Results show how lithological discontinuities influence the depth gradients and that properties inherited from substrate should be distinguished, if possible, from those developed by pedogenesis.     

Colluvisols under cultivation in Schleswig-Holstein. 1. Genesis,definition and geo-ecological significance

In Schleswig-Holstein, F.R.G., two typical soil associations from loamy boulder marl and loamy pleistocene sands were mapped and ecologically characterized in order to show the necessity of an adequate classification of Colluvic Cumulic Anthrosols (Colluvisols). More than 50% of the original soils have been altered by erosion. The depth of the colluvic wM horizon ranges between 10 cm and more than 100 cm. The amounts of soil organic matter and plant available nutrients are much higher in the Colluvisols than in the haplic soils. Soil classification does not deal with all these aspects with regard to mapping of colluvic soils. In the German soil classification adequate and ecologically significant definitions and instructions of the nomenclature of colluvic soils are not available. Therefore, a proposal is presented to classify colluvic soils. In addition the threshold value of 0.6% soil organic matter in sandy parent material is too low in order to distinguish a Bv from a M horizon; 1.0% would be a more acceptable value. It would be necessary to investigate yield on erodic, non-erodic and colluvic soils in order to determine the effect of erosion and accumulation on crop yield.     

The "Friedrich-Loeffler-Institut": past, present and future of research in infectious diseases of animals

The Friedrich-Loeffler-Institut, founded in 1910 by Friedrich Loeffler, the discoverer of the first animal virus, foot-and-mouth disease virus, is the oldest virological research facility in the world. Beyond viruses, its area of competence has significantly expanded since its foundation and now also covers bacterial, parasitic and prion diseases of livestock, poultry and aquatic animals. Presently located at four sites within Germany (Insel Riems, Jena,Tübingen,Wusterhausen) the tasks of the institute as delineated in the Animal Disease Act encompass research on infectious animal diseases including zoonoses, import/export examinations, epidemiological studies in case of outbreaks of notifiable animal diseases, acting as reference laboratory for notifiable animal diseases and nationwide quality management of diagnosis of notifiable animal diseases. It is obliged to publish and maintain up-to-date diagnostic regimes for notifiable animal diseases, and it publishes a yearly report on animal health in Germany. With the increasing importance of infectious diseases of animals, in particular those potentially harmful to man (zoonoses), the Friedrich-Loeffler-Institut will be moving into new facilities including laboratories and animal facilities up to the highest biosafety level at its main site Insel Riems on the occasion of its 100th anniversary.     

A stochastic model for simulation of the economic consequences of bovine virus diarrhoea virus infection in a dairy herd

A dynamic, stochastic model simulating the technical and economic consequences of bovine virus diarrhoea virus (BVDV) infections for a dairy cattle herd for use on a personal computer was developed. The production and state changes of the herd were simulated by state changes of the individual cows and heifers. All discrete events at the cow level were triggered stochastically. Each cow and heifer was characterized by state variables such as stage of lactation, parity, oestrous status, decision for culling, milk production potential, and immune status for BVDV. The model was controlled by 170 decision variables describing biologic and management variables including 21 decision variables describing the effect of BVDV infection on the production of the individual animal. Two markedly different scenarios were simulated to demonstrate the behaviour of the developed model and the potentials of the applied modelling principle. The validation problem in relation to the model was discussed. A comparison between real and simulated data using data from a published case report was shown to illustrate how user acceptance can be obtained.     

Molecular evidence for the infection of zoo chimpanzees by pig Ascaris

We here describe the transmission of the pig roundworm, Ascaris suum to chimpanzees maintained in the Copenhagen Zoo, Denmark. Using a technique for whole genome fingerprinting, amplified fragment length polymorphism (AFLP) and the technique PCR restricted fragment length polymorphism (PCR-RFLP) of the internal transcribed spacer region (ITS) of the nuclear ribosomal DNA, the worms from the chimpanzees were compared with Ascaris spp obtained from humans and pigs in order to identify the source of the infection. By the use of different distance and clustering based methods on the AFLP data set the worms from the chimpanzees were assigned to the same cluster as that of the worms from pigs. The PCR-RFLP analysis supported the AFLP results. Therefore, the zoo chimpanzees have required Ascaris infections by cross-infection from pigs. Pigs as a potential source of Ascaris infections for both captive and wild chimpanzees and other animals, therefore needs to be considered and appropriate steps taken to prevent such infection.