A high abundance of massive galaxies 3-6 billion years after the Big Bang

Hierarchical galaxy formation is the model whereby massive galaxies form from an assembly of smaller units. The most massive objects therefore form last. The model succeeds in describing the clustering of galaxies, but the evolutionary history of massive galaxies, as revealed by their visible stars and gas, is not accurately predicted. Near-infrared observations (which allow us to measure the stellar masses of high-redshift galaxies) and deep multi-colour images indicate that a large fraction of the stars in massive galaxies form in the first 5 Gyr (refs 4-7), but uncertainties remain owing to the lack of spectra to confirm the redshifts (which are estimated from the colours) and the role of obscuration by dust. Here we report the results of a spectroscopic redshift survey that probes the most massive and quiescent galaxies back to an era only 3 Gyr after the Big Bang. We find that at least two-thirds of massive galaxies have appeared since this era, but also that a significant fraction of them are already in place in the early Universe.     

Present status of underwater medicine. Review of some challenging problems

Zusammenfassung Es wird eine Übersicht über den gegenwärtigen Stand der Unterwassermedizin gegeben. Besondere Berücksichtigung finden die in jüngster Zeit durchgeführten Forschungen, die die Grundlage für eine Erweiterung der Grenzen des Tieftauchens bereiteten, wie z.B. der 1972 durchgeführte Rekordtauchgang der Comex Gruppe, bei dem eine Tiefe von 2001 Fuss (610 m) in der Kammer erreicht wurde. Nach den in diesem Experiment erhobenen Befunden können ausgewählte und trainierte Taucher in einer Tiefe von 1400 Fuss (427 m) noch gut arbeiten und leben, wenn sie eine Helium-Sauerstoffmischung atmen. Die Ursachen des «Nervösen Hochdruck-Syndromes», sowie die kritische Volumentherorie vonMiller ⁶ als ein Erklärungsversuch für das Fehlen der narkotischen Wirkung von Helium unter hohem Druck im Vergleich zu Stickstoff werden diskutiert.

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This paper was presented in part at the XXI International Congress of Aviation and Space Medicine, September 19, 1973 in Munich (Germany, Fed. Rep.).     

An outline of the varieties of the second-order systems sciences

The systems sciences are based on a universal language of systems which can be used within most academic disciplines in their endeavors for exploring the world. Currently, systems sciences cover a wide variety of different approaches like complex adaptive systems, resilient systems or systems engineering. One of the future extensions of the systems sciences comes through the applications of second-order systems science as a new field of reflexive studies on first-order systems science. This article provides a general background on the relations of first-order science and second-order science in general and then goes on to sketch a basic outline for the second-order systems sciences and their potentials for quality control and for innovations for the first-order systems sciences.     

Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage

Drosophila neuroblasts and ovarian stem cells are well characterized models for stem cell biology. In both cell types, one daughter cell self-renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim-NHL (tripartite motif and Ncl-1, HT2A and Lin-41 domain)-containing protein Brain tumour (Brat) into one of the two daughter cells, ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes 4 transit-amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim-NHL protein Mei-P26 (refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei-P26 expression is low in stem cells but is strongly induced in 16-cell cysts. In mei-P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei-P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute-1, a component of the RISC complex, as a common binding partner of Brat and Mei-P26, and show that Mei-P26 acts by inhibiting the microRNA pathway. Mei-P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.     

A role for Wnt signalling in self-renewal of haematopoietic stem cells

Haematopoietic stem cells (HSCs) have the ability to renew themselves and to give rise to all lineages of the blood; however, the signals that regulate HSC self-renewal remain unclear. Here we show that the Wnt signalling pathway has an important role in this process. Overexpression of activated beta-catenin expands the pool of HSCs in long-term cultures by both phenotype and function. Furthermore, HSCs in their normal microenvironment activate a LEF-1/TCF reporter, which indicates that HCSs respond to Wnt signalling in vivo. To demonstrate the physiological significance of this pathway for HSC proliferation we show that the ectopic expression of axin or a frizzled ligand-binding domain, inhibitors of the Wnt signalling pathway, leads to inhibition of HSC growth in vitro and reduced reconstitution in vivo. Furthermore, activation of Wnt signalling in HSCs induces increased expression of HoxB4 and Notch1, genes previously implicated in self-renewal of HSCs. We conclude that the Wnt signalling pathway is critical for normal HSC homeostasis in vitro and in vivo, and provide insight into a potential molecular hierarchy of regulation of HSC development.     

Recognition of transmembrane helices by the endoplasmic reticulum translocon

Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein-lipid interactions are critical during translocon-mediated membrane insertion.     

Climate (communication arising): impact of land-use change on climate

Urbanization and other changes in land use have an impact on surface-air temperatures. Kalnay and Cai report that the observed surface-temperature trend in part of the United States exceeds the trend in the NCEP/NCAR 50-year reanalysis (NNR) and conclude that changes in land use account for the difference (0.035 degrees C per decade according to their corrected values). Although land-use change may explain some of this discrepancy, the authors do not quantify the impact of the many changes in observational practice that occurred during the analysis period. Our findings indicate that these 'non-climatic' changes have a systematic effect that overwhelms the reported difference in trends and therefore calls Kalnay and Cai's central conclusion into question.     

Optogenetic stimulation of a hippocampal engram activates fear memory recall

A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.