Bericht über die 4. Tagung für Elektronen-mikroskopie des Schweizer Komitees für Optik

Ohne Zusammenfassung     

Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice

Williams syndrome is a neurodevelopmental disorder caused by the hemizygous deletion of 1.6 Mb on human chromosome 7q11.23. This region comprises the gene CYLN2, encoding CLIP-115, a microtubule-binding protein of 115 kD. Using a gene-targeting approach, we provide evidence that mice with haploinsufficiency for Cyln2 have features reminiscent of Williams syndrome, including mild growth deficiency, brain abnormalities, hippocampal dysfunction and particular deficits in motor coordination. Absence of CLIP-115 also leads to increased levels of CLIP-170 (a closely related cytoplasmic linker protein) and dynactin at the tips of growing microtubules. This protein redistribution may affect dynein motor regulation and, together with the loss of CLIP-115-specific functions, underlie neurological alterations in Williams syndrome.     

Novel insights into the biology of interleukin-32

Interleukin (IL)-32 is known as a proinflammatory cytokine that is likely involved in several diseases, including infections, chronic inflammation, and cancer. Since the first report in 2005, IL-32 has been the subject of numerous studies to unravel the biological function of this molecule. For example, silencing of endogenous IL-32 in primary or cell lines of human origin consistently suppressed responses to Toll-like receptors. The protein folding structure of the six isoforms of IL-32 does not resemble that of any classical cytokine and as of this writing, a specific IL-32 receptor has not been identified. Instead, we propose a mechanism by which exposure to extracellular IL-32 or overexpression of the molecule results in binding to intracellular partners that influences functions such as gene expression, cell death, or survival. As such, this review offers insights into the role of IL-32 in several diseases, host defense, inflammation, immune function, and cancer. Finally, possibilities to target IL-32 in several diseases are proposed.     

Biogeography: molecular trails from hitch-hiking snails

Darwin was fascinated by the transportation of land snails across great swathes of open ocean by birds--he even immersed snails in sea water to see how long they would survive. Here we follow a molecular phylogenetic trail that reveals the incredible transequatorial dispersal of the land snail Balea from Europe to the Azores and the Tristan da Cunha islands, and back again. This long-distance dispersal is unexpected for what are proverbially considered the most pedestrian of creatures.     

Catastrophic ape decline in western equatorial Africa

Because rapidly expanding human populations have devastated gorilla (Gorilla gorilla) and common chimpanzee (Pan troglodytes) habitats in East and West Africa, the relatively intact forests of western equatorial Africa have been viewed as the last stronghold of African apes. Gabon and the Republic of Congo alone are thought to hold roughly 80% of the world's gorillas and most of the common chimpanzees. Here we present survey results conservatively indicating that ape populations in Gabon declined by more than half between 1983 and 2000. The primary cause of the decline in ape numbers during this period was commercial hunting, facilitated by the rapid expansion of mechanized logging. Furthermore, Ebola haemorrhagic fever is currently spreading through ape populations in Gabon and Congo and now rivals hunting as a threat to apes. Gorillas and common chimpanzees should be elevated immediately to 'critically endangered' status. Without aggressive investments in law enforcement, protected area management and Ebola prevention, the next decade will see our closest relatives pushed to the brink of extinction.     

High-fidelity projective read-out of a solid-state spin quantum register

Initialization and read-out of coupled quantum systems are essential ingredients for the implementation of quantum algorithms. Single-shot read-out of the state of a multi-quantum-bit (multi-qubit) register would allow direct investigation of quantum correlations (entanglement), and would give access to further key resources such as quantum error correction and deterministic quantum teleportation. Although spins in solids are attractive candidates for scalable quantum information processing, their single-shot detection has been achieved only for isolated qubits. Here we demonstrate the preparation and measurement of a multi-spin quantum register in a low-temperature solid-state system by implementing resonant optical excitation techniques originally developed in atomic physics. We achieve high-fidelity read-out of the electronic spin associated with a single nitrogen-vacancy centre in diamond, and use this read-out to project up to three nearby nuclear spin qubits onto a well-defined state. Conversely, we can distinguish the state of the nuclear spins in a single shot by mapping it onto, and subsequently measuring, the electronic spin. Finally, we show compatibility with qubit control: we demonstrate initialization, coherent manipulation and single-shot read-out in a single experiment on a two-qubit register, using techniques suitable for extension to larger registers. These results pave the way for a test of Bell's inequalities on solid-state spins and the implementation of measurement-based quantum information protocols.     

Deciphering the evolution and metabolism of an anammox bacterium from a community genome

Anaerobic ammonium oxidation (anammox) has become a main focus in oceanography and wastewater treatment. It is also the nitrogen cycle's major remaining biochemical enigma. Among its features, the occurrence of hydrazine as a free intermediate of catabolism, the biosynthesis of ladderane lipids and the role of cytoplasm differentiation are unique in biology. Here we use environmental genomics--the reconstruction of genomic data directly from the environment--to assemble the genome of the uncultured anammox bacterium Kuenenia stuttgartiensis from a complex bioreactor community. The genome data illuminate the evolutionary history of the Planctomycetes and allow us to expose the genetic blueprint of the organism's special properties. Most significantly, we identified candidate genes responsible for ladderane biosynthesis and biological hydrazine metabolism, and discovered unexpected metabolic versatility.     

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25

Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.     

Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal gammadelta T cells

B cells, alphabeta T cells and gammadelta T cells are conserved lymphocyte subtypes encoding their antigen receptors from somatically rearranged genes. alphabeta T cells undergo positive selection in the thymus by engagement of their T cell receptors (TCRs) with self-peptides presented by major histocompatibility complex molecules. The molecules that select gammadelta T cells are unknown. Vgamma5+Vdelta1+ cells comprise 90% of mouse epidermal gammadelta T cells. By mapping and genetic complementation using a strain showing loss of Vgamma5+Vdelta1+ cells due to a failure of thymic selection, we show that this defect is caused by mutation in Skint1, a newly identified gene expressed in thymus and skin that encodes a protein with immunoglobulin-like and transmembrane domains. Skint1 is the prototypic member of a rapidly evolving family of at least 11 genes in mouse, with greatest similarity to the butyrophilin genes. These findings define a new family of proteins mediating key epithelial-immune interactions.