Showing papers by "University of Göttingen published in 2010"

Emerging applications of stimuli-responsive polymer materials

Abstract: Responsive polymer materials can adapt to surrounding environments, regulate transport of ions and molecules, change wettability and adhesion of different species on external stimuli, or convert chemical and biochemical signals into optical, electrical, thermal and mechanical signals, and vice versa. These materials are playing an increasingly important part in a diverse range of applications, such as drug delivery, diagnostics, tissue engineering and 'smart' optical systems, as well as biosensors, microelectromechanical systems, coatings and textiles. We review recent advances and challenges in the developments towards applications of stimuli-responsive polymeric materials that are self-assembled from nanostructured building blocks. We also provide a critical outline of emerging developments.

Review of Particle Physics

Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2158 new measurements from 551 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 108 reviews are many that are new or heavily revised including those on neutrino mass, mixing, and oscillations, QCD, top quark, CKM quark-mixing matrix, V-ud & V-us, V-cb & V-ub, fragmentation functions, particle detectors for accelerator and non-accelerator physics, magnetic monopoles, cosmological parameters, and big bang cosmology.

Silane coupling agents used for natural fiber/polymer composites: A review

Abstract: Natural fiber reinforced polymer composites (NFPCs) provide the customers with more alternatives in the material market due to their unique advantages. Poor fiber–matrix interfacial adhesion may, however, negatively affect the physical and mechanical properties of the resulting composites due to the surface incompatibility between hydrophilic natural fibers and non-polar polymers (thermoplastics and thermosets). A variety of silanes (mostly trialkoxysilanes) have been applied as coupling agents in the NFPCs to promote interfacial adhesion and improve the properties of composites. This paper reviews the recent progress in using silane coupling agents for NFPCs, summarizes the effective silane structures from the silane family, clarifies the interaction mechanisms between natural fibers and polymer matrices, and presents the effects of silane treatments on the mechanical and outdoor performance of the resulting composites.

Experimental phasing with SHELXC/D/E: combining chain tracing with density modification

Abstract: The programs SHELXC, SHELXD and SHELXE are designed to provide simple, robust and efficient experimental phasing of macromolecules by the SAD, MAD, SIR, SIRAS and RIP methods and are particularly suitable for use in automated structure-solution pipelines. This paper gives a general account of experimental phasing using these programs and describes the extension of iterative density modification in SHELXE by the inclusion of automated protein main-chain tracing. This gives a good indication as to whether the structure has been solved and enables interpretable maps to be obtained from poorer starting phases. The autotracing algorithm starts with the location of possible seven-residue α-­helices and common tripeptides. After extension of these fragments in both directions, various criteria are used to decide whether to accept or reject the resulting poly-Ala traces. Noncrystallographic symmetry (NCS) is applied to the traced fragments, not to the density. Further features are the use of a `no-go' map to prevent the traces from passing through heavy atoms or symmetry elements and a splicing technique to combine the best parts of traces (including those generated by NCS) that partly overlap.

Rett syndrome: Revised diagnostic criteria and nomenclature

Abstract: Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. Method RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. Results The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. Interpretation These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research.

A Genome-Wide Association Study Identifies New Psoriasis Susceptibility Loci and an Interaction Between HLA-C and ERAP1

Abstract: To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10⁻⁸ and two loci with a combined P < 5 × 10⁻⁷). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10⁻⁶). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.

Ten years on: a review of recent research on the Job Demand-Control (-Support) model and psychological well-being.

Abstract: In 1999, van der Doef and Maes published a systematic review focusing on the Job-Demand–Control (JDC) model (Karasek, 1979) and the Job Demand–Control (-Support) (JDCS) model (Johnson & Hall, 1988) in relation to psychological well-being. Their review covered the period from 1979 to 1997. The present paper updates and extends this review. Covering research from 83 studies published between 1998 and 2007, our review revealed three major results: First, support for additive effects of demands, control, and social support on general psychological well-being is almost always found if the sample size is sufficient. Second, although there was consistent evidence for additive effects in relation to job-related well-being in cross-sectional studies, support rates were lower in longitudinal data. Thus, reciprocal or reversed causation might account for part of the association between JDC/JDCS dimensions and job-related well-being. Finally, evidence for interactive effects as predicted by the buffer hypoth...

Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice

Abstract: As the human life span increases, the number of people suffering from cognitive decline is rising dramatically. The mechanisms underlying age-associated memory impairment are, however, not understood. Here we show that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation and fail to initiate a hippocampal gene expression program associated with memory consolidation. Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities. Our data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the aging mouse brain.

Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.

Abstract: We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Abstract: Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels However, only a few studies have so far incorporated an explicit food-web perspective In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory This was true both for abundance and species richness of organisms Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores Density and richness of carnivorous taxa was independent of vegetation structure Below-ground responses to plant diversity were consistently weaker than above-ground responses Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades

Comparing the statistics of interstellar turbulence in simulations and observations - Solenoidal versus compressive turbulence forcing

Abstract: Context. Density and velocity fluctuations on virtually all scales observed with modern telescopes show that molecular clouds (MCs) are turbulent. The forcing and structural characteristics of this turbulence are, however, still poorly understood.Aims. To shed light on this subject, we study two limiting cases of turbulence forcing in numerical experiments: solenoidal (divergence-free) forcing and compressive (curl-free) forcing, and compare our results to observations.Methods. We solve the equations of hydrodynamics on grids with up to 10243 cells for purely solenoidal and purely compressive forcing. Eleven lower-resolution models with different forcing mixtures are also analysed.Results. Using Fourier spectra and Δ -variance, we find velocity dispersion-size relations consistent with observations and independent numerical simulations, irrespective of the type of forcing. However, compressive forcing yields stronger compression at the same rms Mach number than solenoidal forcing, resulting in a three times larger standard deviation of volumetric and column density probability distributions (PDFs). We compare our results to different characterisations of several observed regions, and find evidence of different forcing functions. Column density PDFs in the Perseus MC suggest the presence of a mainly compressive forcing agent within a shell, driven by a massive star. Although the PDFs are close to log-normal, they have non-Gaussian skewness and kurtosis caused by intermittency. Centroid velocity increments measured in the Polaris Flare on intermediate scales agree with solenoidal forcing on that scale. However, Δ -variance analysis of the column density in the Polaris Flare suggests that turbulence is driven on large scales, with a significant compressive component on the forcing scale. This indicates that, although likely driven with mostly compressive modes on large scales, turbulence can behave like solenoidal turbulence on smaller scales. Principal component analysis of G216-2.5 and most of the Rosette MC agree with solenoidal forcing, but the interior of an ionised shell within the Rosette MC displays clear signatures of compressive forcing.Conclusions. The strong dependence of the density PDF on the type of forcing must be taken into account in any theory using the PDF to predict properties of star formation. We supply a quantitative description of this dependence. We find that different observed regions show evidence of different mixtures of compressive and solenoidal forcing, with more compressive forcing occurring primarily in swept-up shells. Finally, we emphasise the role of the sonic scale for protostellar core formation, because core formation close to the sonic scale would naturally explain the observed subsonic velocity dispersions of protostellar cores.

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

Abstract: The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.

Biodiversity Differences between Managed and Unmanaged Forests: Meta-Analysis of Species Richness in Europe

Abstract: Past and present pressures on forest resources have led to a drastic decrease in the surface area of unmanaged forests in Europe. Changes in forest structure, composition, and dynamics inevitably lead to changes in the biodiversity of forest-dwelling species. The possible biodiversity gains and losses due to forest management (i.e., anthropogenic pressures related to direct forest resource use), however, have never been assessed at a pan-European scale. We used meta-analysis to review 49 published papers containing 120 individual comparisons of species richness between unmanaged and managed forests throughout Europe. We explored the response of different taxonomic groups and the variability of their response with respect to time since abandonment and intensity of forest management. Species richness was slightly higher in unmanaged than in managed forests. Species dependent on forest cover continuity, deadwood, and large trees (bryophytes, lichens, fungi, saproxylic beetles) and carabids were negatively affected by forest management. In contrast, vascular plant species were favored. The response for birds was heterogeneous and probably depended more on factors such as landscape patterns. The global difference in species richness between unmanaged and managed forests increased with time since abandonment and indicated a gradual recovery of biodiversity. Clearcut forests in which the composition of tree species changed had the strongest effect on species richness, but the effects of different types of management on taxa could not be assessed in a robust way because of low numbers of replications in the management-intensity classes. Our results show that some taxa are more affected by forestry than others, but there is a need for research into poorly studied species groups in Europe and in particular locations. Our meta-analysis supports the need for a coordinated European research network to study and monitor the biodiversity of different taxa in managed and unmanaged forests.

The MUSE second-generation VLT instrument

Abstract: Summary: The Multi Unit Spectroscopic Explorer (MUSE) is a second-generation VLT panoramic integral-field spectrograph currently in manufacturing, assembly and integration phase. MUSE has a field of 1x1 arcmin2 sampled at 0.2x0.2 arcsec2 and is assisted by the VLT ground layer adaptive optics ESO facility using four laser guide stars. The instrument is a large assembly of 24 identical high performance integral field units, each one composed of an advanced image slicer, a spectrograph and a 4kx4k detector. In this paper we review the progress of the manufacturing and report the performance achieved with the first integral field unit.

Observation of a centrality-dependent dijet asymmetry in lead-lead collisions at √sNN=2.76 Tev with the ATLAS detector at the LHC

Abstract: By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

Abstract: Background 1Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. Principal Findings We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. Significance Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

Périgord black truffle genome uncovers evolutionary origins and mechanisms of symbiosis

Abstract: The Perigord black truffle ($Tuber\ melanosporum$ Vittad.) and the Piedmont white truffle dominate today's truffle market. The hypogeous fruiting body of $T.\ melanosporum$ is a gastronomic delicacy produced by an ectomycorrhizal symbiont endemic to calcareous soils in southern Europe. The worldwide demand for this truffle has fuelled intense efforts at cultivation. Identification of processes that condition and trigger fruit body and symbiosis formation, ultimately leading to efficient crop production, will be facilitated by a thorough analysis of truffle genomic traits. In the ectomycorrhizal $Laccaria\ bicolor$, the expansion of gene families may have acted as a 'symbiosis toolbox'. This feature may however reflect evolution of this particular taxon and not a general trait shared by all ectomycorrhizal species. To get a better understanding of the biology and evolution of the ectomycorrhizal symbiosis, we report here the sequence of the haploid genome of $T.\ melanosporum$, which at $\sim$125 megabases is the largest and most complex fungal genome sequenced so far. This expansion results from a proliferation of transposable elements accounting for $\sim$58% of the genome. In contrast, this genome only contains $\sim$7,500 protein-coding genes with very rare multigene families. It lacks large sets of carbohydrate cleaving enzymes, but a few of them involved in degradation of plant cell walls are induced in symbiotic tissues. The latter feature and the upregulation of genes encoding for lipases and multicopper oxidases suggest that $T.\ melanosporum$ degrades its host cell walls during colonization. Symbiosis induces an increased expression of carbohydrate and amino acid transporters in both $L.\ bicolor$ and $T.\ melanosporum$, but the comparison of genomic traits in the two ectomycorrhizal fungi showed that genetic predispositions for symbiosis $-$'the symbiosis toolbox'$-$ evolved along different ways in ascomycetes and basidiomycetes

Physics of bubble oscillations

Abstract: Bubbles in liquids, soft and squeezy objects made of gas and vapour, yet so strong as to destroy any material and so mysterious as at times turning into tiny light bulbs, are the topic of the present report. Bubbles respond to pressure forces and reveal their full potential when periodically driven by sound waves. The basic equations for nonlinear bubble oscillation in sound fields are given, together with a survey of typical solutions. A bubble in a liquid can be considered as a representative example from nonlinear dynamical systems theory with its resonances, multiple attractors with their basins, bifurcations to chaos and not yet fully describable behaviour due to infinite complexity. Three stability conditions are treated for stable trapping of bubbles in standing sound fields: positional, spherical and diffusional stability. Chemical reactions may become important in that respect, when reacting gases fill the bubble, but the chemistry of bubbles is just touched upon and is beyond the scope of the present report. Bubble collapse, the runaway shrinking of a bubble, is presented in its current state of knowledge. Pressures and temperatures that are reached at this occasion are discussed, as well as the light emission in the form of short flashes. Aspherical bubble collapse, as for instance enforced by boundaries nearby, mitigates most of the phenomena encountered in spherical collapse, but introduces a new effect: jet formation, the self-piercing of a bubble with a high velocity liquid jet. Examples of this phenomenon are given from light induced bubbles. Two oscillating bubbles attract or repel each other, depending on their oscillations and their distance. Upon approaching, attraction may change to repulsion and vice versa. When being close, they also shoot self-piercing jets at each other. Systems of bubbles are treated as they appear after shock wave passage through a liquid and with their branched filaments that they attain in standing sound fields. The N-bubble problem is formulated in the spirit of the n-body problem of astrophysics, but with more complicated interaction forces. Simulations are compared with three-dimensional bubble dynamics obtained by stereoscopic high speed digital videography.

Methylation determines fibroblast activation and fibrogenesis in the kidney

Abstract: Fibrogenesis is a pathological wound repair process that fails to cease, even when the initial insult has been removed. Fibroblasts are principal mediators of fibrosis, and fibroblasts from fibrotic tissues fail to return to their quiescent stage, including when cultured in vitro. In a search for underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis is caused by epigenetic modifications. We demonstrate here that hypermethylation of RASAL1, encoding an inhibitor of the Ras oncoprotein, is associated with the perpetuation of fibroblast activation and fibrogenesis in the kidney. RASAL1 hypermethylation is mediated by the methyltransferase Dnmt1 in renal fibrogenesis, and kidney fibrosis is ameliorated in Dnmt1(+/-) heterozygous mice. These studies demonstrate that epigenetic modifications may provide a molecular basis for perpetuated fibroblast activation and fibrogenesis in the kidney.

A framework for delineating biogeographical regions based on species distributions

Abstract: Aim Biogeographical regionalizations, such as zoogeographical regions, floristic kingdoms or ecoregions, represent categorizations central to many basic and applied questions in biogeography, ecology, evolution and conservation. Traditionally established by experts based on qualitative evidence, the lack of transparency and quantitative support has set constraints on their utility. The recent availability of global species range maps, novel multivariate techniques and enhanced computational power now enable a quantitative scrutiny and extension of biogeographical regionalizations that will facilitate new and more rigorous uses. In this paper we develop and illustrate a methodological roadmap for species-level biogeographical regionalizations at the global scale and apply it to mammals. Location Global. Methods We explore the relative usefulness of ordination and clustering methods and validation techniques. The performance of nine different clustering algorithms is tested at different taxonomic levels. The grain of regionalization (i.e. the number of clusters) will usually be driven by the purpose of the study, but we present several approaches that provide guidance. Results Non-metric multidimensional scaling offers a valuable first step in identifying and illustrating biogeographical transition zones. For the clustering of regions, the nine different hierarchical clustering methods varied greatly in utility, with UPGMA (unweighted pair-group method using arithmetic averages) agglomerative hierarchical clustering having consistently the best performance. The UPGMA approach allows a tree-like phenetic representation of the relative distances of regions and can be applied at different levels of taxonomic resolution. We find that the new quantitative biogeographical regions exhibit both striking similarities to and differences from the classic primary geographical divisions of the world’s biota. Specifically, our results provide evidence that the Sahara, northern Africa, the Arabian Peninsula and parts of the Middle East should be regarded as part of the Afrotropics. Further, the position of the New Guinean continental shelf, Lydekker’s Line, is supported as an appropriate border to separate the Oriental and Australian regions. Main conclusions We propose that this sort of new, quantitative delineation and relationship assessment across taxonomic and geographical grains is likely to offer opportunities for more rigorous inference in historical and ecological biogeography and conservation.

The importance of wood traits and hydraulic conductance for the performance and life history strategies of 42 rainforest tree species.

Abstract: Summary •In a comparative study of 42 rainforest tree species we examined relationships amongst wood traits, diameter growth and survival of large trees in the field, and shade tolerance and adult stature of the species •The species show two orthogonal axes of trait variation: a primary axis related to the vessel size–number trade-off (reflecting investment in hydraulic conductance vs hydraulic safety) and a secondary axis related to investment in parenchyma vs fibres (storage vs strength) Across species, growth rate was positively related to vessel diameter and potential specific hydraulic conductance (Kp), and negatively related to wood density Survival rate was only positively related to wood density •Light-demanding species were characterized by low wood and vessel density and wide vessels Tall species were characterized by wide vessels with low density and large Kp Hydraulic traits were more closely associated with adult stature than with light demand, possibly because tall canopy species experience more drought stress and face a higher cavitation risk •Vessel traits affect growth and wood density affects growth and survival of large trees in the field Vessel traits and wood density are therefore important components of the performance and life history strategies of tropical tree species

The synaptic pathology of α-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia

Abstract: Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are usually associated with loss of dopaminergic neurons. Loss of substantia nigra neurons and presence of Lewy body inclusions in some of the remaining neurons are the hallmark pathology seen in the final stages of the disease. Attempts to correlate Lewy body pathology to either cell death or severity of clinical symptoms, however, have not been successful. While the pathophysiology of the neurodegenerative process can hardly be explained by Lewy bodies, the clinical symptoms do indicate a degenerative process located at the presynapse resulting in a neurotransmitter deficiency. Recently it was shown that 90% or even more of α-synuclein aggregates in DLB cases were located at the presynapses in the form of very small deposits. In parallel, dendritic spines are retracted, whereas the presynapses are relatively preserved, suggesting a neurotransmitter deprivation. The same α-synuclein pathology can be demonstrated for PD. These findings give rise to the notion that not cell death but rather α-synuclein aggregate-related synaptic dysfunction causes the neurodegeneration. This opens new perspectives for understanding PD and DLB. If presynaptic α-synuclein aggregation, not neuronal loss, is the key issue of the neurodegenerative process, then PD and DLB may eventually be treatable in the future. The disease may progress via trans-synaptical spread, suggesting that stem cell transplants are of limited use. Future therapies may focus on the regeneration of synapses.

Draft genome sequence of the oilseed species Ricinus communis

Abstract: Castor bean (Ricinus communis) is an oilseed crop that belongs to the spurge (Euphorbiaceae) family, which comprises approximately 6,300 species that include cassava (Manihot esculenta), rubber tree (Hevea brasiliensis) and physic nut (Jatropha curcas). It is primarily of economic interest as a source of castor oil, used for the production of high-quality lubricants because of its high proportion of the unusual fatty acid ricinoleic acid. However, castor bean genomics is also relevant to biosecurity as the seeds contain high levels of ricin, a highly toxic, ribosome-inactivating protein. Here we report the draft genome sequence of castor bean (4.6-fold coverage), the first for a member of the Euphorbiaceae. Whereas most of the key genes involved in oil synthesis and turnover are single copy, the number of members of the ricin gene family is larger than previously thought. Comparative genomics analysis suggests the presence of an ancient hexaploidization event that is conserved across the dicotyledonous lineage.

Genome sequence of the model mushroom Schizophyllum commune

Abstract: Much remains to be learned about the biology of mushroom-forming fungi, which are an important source of food, secondary metabolites and industrial enzymes. The wood-degrading fungus Schizophyllum commune is both a genetically tractable model for studying mushroom development and a likely source of enzymes capable of efficient degradation of lignocellulosic biomass. Comparative analyses of its 38.5-megabase genome, which encodes 13,210 predicted genes, reveal the species's unique wood-degrading machinery. One-third of the 471 genes predicted to encode transcription factors are differentially expressed during sexual development of S. commune. Whereas inactivation of one of these, fst4, prevented mushroom formation, inactivation of another, fst3, resulted in more, albeit smaller, mushrooms than in the wild-type fungus. Antisense transcripts may also have a role in the formation of fruiting bodies. Better insight into the mechanisms underlying mushroom formation should affect commercial production of mushrooms and their industrial use for producing enzymes and pharmaceuticals.

Meta-Analysis of Genome-Wide Association Studies of Attention- Deficit/Hyperactivity Disorder

Abstract: Objective Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. Method We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. Results No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. Conclusions Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability.

Sequencing of Culex quinquefasciatus Establishes a Platform for Mosquito Comparative Genomics

Abstract: Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification.

Antiferromagnetic Mott insulating state in single crystals of the honeycomb lattice material Na 2 IrO 3

Abstract: We have synthesized single crystals of ${\text{Na}}_{2}{\text{IrO}}_{3}$ and studied their structure, transport, magnetic, and thermal properties using powder x-ray diffraction, electrical resistivity, isothermal magnetization $M$ versus magnetic field $H$, magnetic susceptibility $\ensuremath{\chi}$ versus temperature $T$, and heat capacity $C$ versus $T$ measurements. ${\text{Na}}_{2}{\text{IrO}}_{3}$ crystallizes in the monoclinic $C2/c$ (No. 15) type structure which is made up of Na and ${\text{NaIr}}_{2}{\text{O}}_{6}$ layers alternately stacked along the $c$ axis. The $\ensuremath{\chi}(T)$ data show Curie-Weiss behavior at high $Tg200\text{ }\text{K}$ with an effective moment ${\ensuremath{\mu}}_{\text{eff}}=1.82(1){\ensuremath{\mu}}_{\text{B}}$ indicating an effective spin ${S}_{\text{eff}}=1/2$ on the ${\text{Ir}}^{4+}$ moments. A large Weiss temperature $\ensuremath{\theta}=\ensuremath{-}116(3)\text{ }\text{K}$ indicates substantial antiferromagnetic interactions between these ${S}_{\text{eff}}=1/2$, ${\text{Ir}}^{4+}$ moments. Anomalies in $\ensuremath{\chi}(T)$ and $C(T)$ data indicate that ${\text{Na}}_{2}{\text{IrO}}_{3}$ undergoes a transition into a long-range antiferromagnetically ordered state below ${T}_{\text{N}}=15\text{ }\text{K}$. The magnetic entropy at ${T}_{\text{N}}$ is only about 20% of what is expected for ${S}_{\text{eff}}=1/2$ moment ordering. The reduced entropy and the large ratio $\ensuremath{\theta}/{T}_{N}\ensuremath{\approx}8$ suggest geometrical magnetic frustration and/or low-dimensional magnetic interactions in ${\text{Na}}_{2}{\text{IrO}}_{3}$. In plane resistivity measurements show insulating behavior. This behavior together with the local-moment magnetism indicates that bulk ${\text{Na}}_{2}{\text{IrO}}_{3}$ is a Mott insulator.