Comprehensive analysis of the chromatin landscape in Drosophila melanogaster

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.     

Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit

Spatial asymmetries in neural connectivity have an important role in creating basic building blocks of neuronal processing. A key circuit module of directionally selective (DS) retinal ganglion cells is a spatially asymmetric inhibitory input from starburst amacrine cells. It is not known how and when this circuit asymmetry is established during development. Here we photostimulate mouse starburst cells targeted with channelrhodopsin-2 (refs 6-8) while recording from a single genetically labelled type of DS cell. We follow the spatial distribution of synaptic strengths between starburst and DS cells during early postnatal development before these neurons can respond to a physiological light stimulus, and confirm connectivity by monosynaptically restricted trans-synaptic rabies viral tracing. We show that asymmetry develops rapidly over a 2-day period through an intermediate state in which random or symmetric synaptic connections have been established. The development of asymmetry involves the spatially selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial distribution of excitatory synaptic inputs from starburst cells is significantly more symmetric than that of the inhibitory inputs at the end of this developmental period. Our work demonstrates a rapid developmental switch from a symmetric to asymmetric input distribution for inhibition in the neural circuit of a principal cell.     

Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7

Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics.     

Molecular phylogenetic evidence that the Chinese viviparid genus Margarya (Gastropoda: Viviparidae) is polyphyletic

We investigated the phylogeny of the viviparid genus Margarya,endemic to Yunnan,China,using two mitochondrial gene fragments(COI and 16S rRNA).The molecular phylogeny based on the combined dataset indicates that Margarya is polyphyletic,as two of the three well-supported clades containing species of Margarya also comprise species from other viviparid genera.In one clade,sequences of four species of Margarya even cluster indiscriminately with those of two species of Cipangopaludina,indicating that the current state of Asian viviparid taxonomy needs to be revised.Additionally,these data suggest that shell evolution in viviparids is complex,as even the large and strongly sculptured shells of Margarya,which are outstanding among Asian viviparids,can apparently be easily converted to simple smooth shells.The molecular data also indicate that the species status of the six extant species of Margarya should be re-assessed.     

A Note on Knowledge Creation in Open-Source Software Projects: What Can We Learn from Luhmann’s Theory of Social Systems?

We use the sociological systems theory proposed by Niklas Luhmann to complement a socially-oriented view of knowledge with the role of technical infrastructure in knowledge creation. We highlight the self-referential character of knowledge creation and draw upon illustrative examples from open-source software. We discuss why knowledge creation processes are often prone to breakdown and propose three conditions that may stabilize knowledge creation processes: perceptibility, systemic memory, and modularity.     

Multiple ionization of atom clusters by intense soft X-rays from a free-electron laser

Intense radiation from lasers has opened up many new areas of research in physics and chemistry, and has revolutionized optical technology. So far, most work in the field of nonlinear processes has been restricted to infrared, visible and ultraviolet light, although progress in the development of X-ray lasers has been made recently. With the advent of a free-electron laser in the soft-X-ray regime below 100 nm wavelength, a new light source is now available for experiments with intense, short-wavelength radiation that could be used to obtain deeper insights into the structure of matter. Other free-electron sources with even shorter wavelengths are planned for the future. Here we present initial results from a study of the interaction of soft X-ray radiation, generated by a free-electron laser, with Xe atoms and clusters. We find that, whereas Xe atoms become only singly ionized by the absorption of single photons, absorption in clusters is strongly enhanced. On average, each atom in large clusters absorbs up to 400 eV, corresponding to 30 photons. We suggest that the clusters are heated up and electrons are emitted after acquiring sufficient energy. The clusters finally disintegrate completely by Coulomb explosion.     

Altruistic punishment in humans.

Human cooperation is an evolutionary puzzle. Unlike other creatures, people frequently cooperate with genetically unrelated strangers, often in large groups, with people they will never meet again, and when reputation gains are small or absent. These patterns of cooperation cannot be explained by the nepotistic motives associated with the evolutionary theory of kin selection and the selfish motives associated with signalling theory or the theory of reciprocal altruism. Here we show experimentally that the altruistic punishment of defectors is a key motive for the explanation of cooperation. Altruistic punishment means that individuals punish, although the punishment is costly for them and yields no material gain. We show that cooperation flourishes if altruistic punishment is possible, and breaks down if it is ruled out. The evidence indicates that negative emotions towards defectors are the proximate mechanism behind altruistic punishment. These results suggest that future study of the evolution of human cooperation should include a strong focus on explaining altruistic punishment.     

Depletion and repletion of noradrenaline in adrenergic nerves of the rat after decaborane treatment

Zusammenfassung Mit Hilfe der Fluoreszenz-Technik werden die Veränderungen in sympathischen Fasern der Ratteniris nach Noradrenalin-Depletion durch Boron-Hydrid Decarboran (Dopa-Dekarboxylase-Hemmer) analysiert.

---

---

This work has been supported by grants from the Swedish Medical Research Council under project No. B70-14x-97-06B, B70-14x-711-05B and Knut and Alice Wallenberg Foundation.     

Sex attractant of the larch bud moth found by electroantennogram method

Zusammenfassung Mit Hilfe der Antennogramm-Methode wurdetrans-11-Tetracedenylacetat als spezifisches Attraktans für Männchen des LärchenwicklersZeiraphera diniana bestimmt. In geeigneter Konzentration ist die Attraktivität der synthetischen Substanz derjenigen virginer Weibchen ebenbürtig.

---

---

This research was supported in part by Environmental Protection Agency Grant No. EP-00802 and by the Rockefeller Foundation.

---

Contribution No. 46 of the research team for the investigation of the population dynamics of the larch bud moth, directed by Professor Dr.P. Bovey. The research was aided by the Swiss National Funds for Scientific Research.