Anthropogenic ocean acidification over the twenty-first century and its impact on calcifying organisms

Today's surface ocean is saturated with respect to calcium carbonate, but increasing atmospheric carbon dioxide concentrations are reducing ocean pH and carbonate ion concentrations, and thus the level of calcium carbonate saturation. Experimental evidence suggests that if these trends continue, key marine organisms--such as corals and some plankton--will have difficulty maintaining their external calcium carbonate skeletons. Here we use 13 models of the ocean-carbon cycle to assess calcium carbonate saturation under the IS92a 'business-as-usual' scenario for future emissions of anthropogenic carbon dioxide. In our projections, Southern Ocean surface waters will begin to become undersaturated with respect to aragonite, a metastable form of calcium carbonate, by the year 2050. By 2100, this undersaturation could extend throughout the entire Southern Ocean and into the subarctic Pacific Ocean. When live pteropods were exposed to our predicted level of undersaturation during a two-day shipboard experiment, their aragonite shells showed notable dissolution. Our findings indicate that conditions detrimental to high-latitude ecosystems could develop within decades, not centuries as suggested previously.     

Crystal structure of the ligand-free G-protein-coupled receptor opsin

In the G-protein-coupled receptor (GPCR) rhodopsin, the inactivating ligand 11-cis-retinal is bound in the seven-transmembrane helix (TM) bundle and is cis/trans isomerized by light to form active metarhodopsin II. With metarhodopsin II decay, all-trans-retinal is released, and opsin is reloaded with new 11-cis-retinal. Here we present the crystal structure of ligand-free native opsin from bovine retinal rod cells at 2.9 ?ngstr?m (A) resolution. Compared to rhodopsin, opsin shows prominent structural changes in the conserved E(D)RY and NPxxY(x)(5,6)F regions and in TM5-TM7. At the cytoplasmic side, TM6 is tilted outwards by 6-7 A, whereas the helix structure of TM5 is more elongated and close to TM6. These structural changes, some of which were attributed to an active GPCR state, reorganize the empty retinal-binding pocket to disclose two openings that may serve the entry and exit of retinal. The opsin structure sheds new light on ligand binding to GPCRs and on GPCR activation.     

Platelet-derived chemokines: pathophysiology and therapeutic aspects

The identification of chemokines in blood platelets has strengthened our view of these cells as participants in immune host defense. Platelet chemokines representing prestored and rapidly releasable proteins may play a major role as first-line inflammatory mediators. This is evident from their capability to recruit early inflammatory cells such as neutrophil granulocytes and monocytes and even to exhibit direct antimicrobial activity. However, insight is growing that platelet chemokines may be also long-term regulators, e.g., by activating T lymphocytes, by modulating the formation of endothelium and even thrombocytopoiesis itself. This review deals with the individual and cooperative functionality of platelet chemokines, as well as their potential as a basis for therapeutic intervention in the pathology of inflammation, infection, allergy and tumors. Within this context, therapeutic strategies based on the use of antibodies, modified chemokines, chemokine-binding proteins and chemokine receptor antagonists as well as first clinical studies will be addressed.     

Using human pluripotent stem cells to untangle neurodegenerative disease mechanisms

Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew indefinitely, while maintaining the capacity to differentiate into all cell types of the nervous system. While human pluripotent cell-based therapies are unlikely to arise soon, these cells can currently be used as an inexhaustible source of committed neurons to perform high-throughput screening and safety testing of new candidate drugs. Here, we describe critically the available methods and molecular factors that are used to direct the differentiation of hES or hiPS into specific neurons. In addition, we discuss how the availability of patient-specific hiPS offers a unique opportunity to model inheritable neurodegenerative diseases and untangle their pathological mechanisms, or to validate drugs that would prevent the onset or the progression of these neurological disorders.     

Parochial altruism in humans

Social norms and the associated altruistic behaviours are decisive for the evolution of human cooperation and the maintenance of social order, and they affect family life, politics and economic interactions. However, as altruistic norm compliance and norm enforcement often emerge in the context of inter-group conflicts, they are likely to be shaped by parochialism--a preference for favouring the members of one's ethnic, racial or language group. We have conducted punishment experiments, which allow 'impartial' observers to punish norm violators, with indigenous groups in Papua New Guinea. Here we show that these experiments confirm the prediction of parochialism. We found that punishers protect ingroup victims--who suffer from a norm violation--much more than they do outgroup victims, regardless of the norm violator's group affiliation. Norm violators also expect that punishers will be lenient if the latter belong to their social group. As a consequence, norm violations occur more often if the punisher and the norm violator belong to the same group. Our results are puzzling for evolutionary multi-level selection theories based on selective group extinction as well as for theories of individual selection; they also indicate the need to explicitly examine the interactions between individuals stemming from different groups in evolutionary models.     

Amplification of chirality in two-dimensional enantiomorphous lattices

The concept of chirality dates back to 1848, when Pasteur manually separated left-handed from right-handed sodium ammonium tartrate crystals. Crystallization is still an important means for separating chiral molecules into their two different mirror-image isomers (enantiomers), yet remains poorly understood. For example, there are no firm rules to predict whether a particular pair of chiral partners will follow the behaviour of the vast majority of chiral molecules and crystallize together as racemic crystals, or as separate enantiomers. A somewhat simpler and more tractable version of this phenomenon is crystallization in two dimensions, such as the formation of surface structures by adsorbed molecules. The relatively simple spatial molecular arrangement of these systems makes it easier to study the effects of specific chiral interactions; moreover, chiral assembly and recognition processes can be observed directly and with molecular resolution using scanning tunnelling microscopy. The enantioseparation of chiral molecules in two dimensions is expected to occur more readily because planar confinement excludes some bulk crystal symmetry elements and enhances chiral interactions; however, many surface structures have been found to be racemic. Here we show that the chiral hydrocarbon heptahelicene on a Cu111 surface does not undergo two-dimensional spontaneous resolution into enantiomers, but still shows enantiomorphism on a mesoscopic length scale that is readily amplified. That is, we observe formation of racemic heptahelicene domains with non-superimposable mirror-like lattice structures, with a small excess of one of the heptahelicene enantiomers suppressing the formation of one domain type. Similar to the induction of homochirality in achiral enantiomorphous monolayers by a chiral modifier, a small enantiomeric excess suffices to ensure that the entire molecular monolayer consists of domains having only one of two possible, non-superimposable, mirror-like lattice structures.     

cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes

Organogenesis is dependent on the formation of distinct cell types within the embryo. Important to this process are the hox genes, which are believed to confer positional identities to cells along the anteroposterior axis. Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing hoxb7a or hoxa9a but not hoxb8a, indicating that the haematopoietic defect results from perturbations in specific hox genes. Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression. Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis.     

Requirement for mast cell growth factor for primordial germ cell survival in culture.

Mast-cell growth factor (MGF) is encoded by the murine steel (Sl) locus and is a ligand for the tyrosine kinase receptor protein encoded by the proto-oncogene c-kit at the murine dominant white spotting (W) locus. Mutations at both these loci affect mast cells, primordial germ cells (PGCs), haemopoietic stem cells and melanocytes. In many Sl and W mutants, the rapid proliferation of PGC that normally occurs between day 7 and 13.5 of embryonic development fails to occur. As c-kit is expressed in PGCs while MGF is expressed in the surrounding mesenchyme, MGF might promote the proliferation of PGCs. Here we report that MGF is essential for PGC survival in culture, but does not stimulate PGC proliferation. Moreover, whereas both the transmembrane and soluble proteolytic cleavage forms of MGF stimulate mast-cell proliferation, soluble MGF has a relatively limited ability to support survival of PGCs in culture, thus explaining the sterility in mice carrying the steel-dickie (Sld) mutation, which encodes only a soluble form of MGF, and providing a functional role for a transmembrane growth factor.