Assessing local impacts of water use on human health: evaluation of water footprint models in the Province Punjab,Pakistan

The International Journal of Life Cycle Assessment - The water footprint (WF) method is widely applied to quantify water use along the life cycle of products and organizations and to evaluate the...     

Porous assembly of an antifungal protein mediated by zinc and sulfonato-calix[8]arene

Controlled protein assembly holds great potential in the fabrication of biohybrid materials. However, the structural diversity and complexity of proteins present an obstacle to controlled assembly. Supramolecular chemistry is a possible solution as it offers tools to mediate self-assembly with molecular precision. This paper deals with the calixarene- and zinc-mediated assembly and crystallization of the histidine-rich Penicillium chrysogenum antifungal protein B (PAFB). We report crystal structures of pure PAFB, PAFB in complex with Zn²⁺, and the ternary complex of PAFB, Zn²⁺ and sulfonato-calix[8]arene (sclx₈). A comparison of the three crystal structures revealed the structural plasticity of PAFB. While the flexible and highly anionic sclx₈ resulted in large molecular weight aggregates of PAFB in solution, diffraction-quality crystals of PAFB-sclx₈ were not obtained. We report crystals of PAFB-Zn²⁺-sclx₈ in which a trinuclear zinc cluster occurred adjacent to a calixarene binding site. Interestingly, the combination of sclx₈ complexation and zinc coordination resulted in a porous framework with channels of circa 2 nm diameter. Detailed analysis of the crystal structure highlighted novel molecular recognition features. This research enriches the set of supramolecular interactions available to promote protein assembly.     

Archaeal symbionts and parasites

Several species of Archaea are involved in symbiotic or parasitic associations with representatives of Eukarya, Bacteria and other Archaea. Eukaryal interactions include different members of methanogens, found in the gut of arthropods, in the rumen of cattle, and in the human intestine, while Cenarchaeum symbiosum is a partner of a marine sponge. Examples for bacterial-archaeal associations are the anaerobic methane oxidation consortia and the SM1 Euryarchaeon with its highly unusual 'hami' as extracellular appendages. The so far only known and cultivated association between two Archaea is composed of Nanoarchaeum equitans and its obligate host Ignicoccus hospitalis. All these consortia can often not be assigned to the 'classical' concepts of mutalism, commensialism or parasitism and represent highly specialized interspecies associations.     

Inhibition of leukotriene receptors boosts neural progenitor proliferation

Neural stem and progenitor cells serve as a reservoir for new neurons in the adult brain throughout lifetime. One of the critical steps determining the net production of new neurons is neural progenitor proliferation, which needs to be tightly controlled. Since inflammation has detrimental effects on neurogenesis and the 5-lipoxygenase/leukotriene pathway is involved in inflammatory processes, we investigated the effects of leukotrienes and montelukast, a small molecule inhibitor of the leukotriene receptors CysLT(1)R and GPR17, on neural stem and progenitor cell proliferation. We demonstrate expression of the leukotriene receptor GPR17 by neural progenitors and by neural stem cells. Stimulation with excess amounts of leukotrienes did not affect progenitor proliferation, whereas blockade of GPR17 with montelukast strongly elevated neural stem and progenitor proliferation, while maintaining their differentiation fate and potential. This effect was associated with increased ERK1/2 phosphorylation suggesting an involvement of the EGF signaling cascade. Based on our results, montelukast and the inhibition of the 5-LOX pathway might be potent candidates for future therapies employing neurogenesis to promote structural and functional improvement in neurodegeneration, neuropsychiatric disease and ageing.     

DOTA-amide lanthanide tag for reliable generation of pseudocontact shifts in protein NMR spectra

Structural studies of proteins and protein-ligand complexes by nuclear magnetic resonance (NMR) spectroscopy can be greatly enhanced by site-specific attachment of lanthanide ions to create paramagnetic centers. In particular, pseudocontact shifts (PCS) generated by paramagnetic lanthanides contain important and unique long-range structure information. Here, we present a high-affinity lanthanide binding tag that can be attached to single cysteine residues of proteins. The new tag has many advantageous features that are not available in this combination from previously published tags: (i) it binds lanthanide ions very tightly, minimizing the generation of nonspecific effects, (ii) it produces PCSs with high reliability as its bulkiness prevents complete motional averaging of PCSs, (iii) it can be attached to single cysteine residues, alleviating the need of detailed prior knowledge of the 3D structure of the target protein, and (iv) it does not display conformational exchange phenomena that would increase the number of signals in the NMR spectrum. The performance of the tag is demonstrated with the N-terminal domain of the E. coli arginine repressor and the A28C mutant of human ubiquitin.     

Metrics on multilabeled trees: interrelationships and diameter bounds

Multilabeled trees or MUL-trees, for short, are trees whose leaves are labeled by elements of some nonempty finite set X such that more than one leaf may be labeled by the same element of X. This class of trees includes phylogenetic trees and tree shapes. MUL-trees arise naturally in, for example, biogeography and gene evolution studies and also in the area of phylogenetic network reconstruction. In this paper, we introduce novel metrics which may be used to compare MUL-trees, most of which generalize well-known metrics on phylogenetic trees and tree shapes. These metrics can be used, for example, to better understand the space of MUL-trees or to help visualize collections of MUL-trees. In addition, we describe some relationships between the MUL-tree metrics that we present and also give some novel diameter bounds for these metrics. We conclude by briefly discussing some open problems as well as pointing out how MUL-tree metrics may be used to define metrics on the space of phylogenetic networks.