NMR analysis of a 900K GroEL GroES complex

Biomacromolecular structures with a relative molecular mass (M(r)) of 50,000 to 100,000 (50K 100K) have been generally considered to be inaccessible to analysis by solution NMR spectroscopy. Here we report spectra recorded from bacterial chaperonin complexes ten times this size limit (up to M(r) 900K) using the techniques of transverse relaxation-optimized spectroscopy and cross-correlated relaxation-enhanced polarization transfer. These techniques prevent deterioration of the NMR spectra by the rapid transverse relaxation of the magnetization to which large, slowly tumbling molecules are otherwise subject. We tested the resolving power of these techniques by examining the isotope-labelled homoheptameric co-chaperonin GroES (M(r) 72K), either free in solution or in complex with the homotetradecameric chaperonin GroEL (M(r) 800K) or with the single-ring GroEL variant SR1 (M(r) 400K). Most amino acids of GroES show the same resonances whether free in solution or in complex with chaperonin; however, residues 17 32 show large chemical shift changes on binding. These amino acids belong to a mobile loop region of GroES that forms contacts with GroEL. This establishes the utility of these techniques for solution NMR studies that should permit the exploration of structure, dynamics and interactions in large macromolecular complexes.     

Climate-mediated energetic constraints on the distribution of hibernating mammals

To predict the consequences of human-induced global climate change, we need to understand how climate is linked to biogeography. Energetic constraints are commonly invoked to explain animal distributions, and physiological parameters are known to vary along distributional gradients. But the causal nature of the links between climate and animal biogeography remain largely obscure. Here we develop a bioenergetic model that predicts the feasibility of mammalian hibernation under different climatic conditions. As an example, we use the well-quantified hibernation energetics of the little brown bat (Myotis lucifugus) to parameterize the model. Our model predicts pronounced effects of ambient temperature on total winter energy requirements, and a relatively narrow combination of hibernaculum temperatures and winter lengths permitting successful hibernation. Microhabitat and northern distribution limits of M. lucifugus are consistent with model predictions, suggesting that the thermal dependence of hibernation energetics constrains the biogeography of this species. Integrating projections of climate change into our model predicts a pronounced northward range expansion of hibernating bats within the next 80 years. Bioenergetics can provide the simple link between climate and biogeography needed to predict the consequences of climate change.     

Local dispersal promotes biodiversity in a real-life game of rock-paper-scissors

One of the central aims of ecology is to identify mechanisms that maintain biodiversity. Numerous theoretical models have shown that competing species can coexist if ecological processes such as dispersal, movement, and interaction occur over small spatial scales. In particular, this may be the case for non-transitive communities, that is, those without strict competitive hierarchies. The classic non-transitive system involves a community of three competing species satisfying a relationship similar to the children's game rock-paper-scissors, where rock crushes scissors, scissors cuts paper, and paper covers rock. Such relationships have been demonstrated in several natural systems. Some models predict that local interaction and dispersal are sufficient to ensure coexistence of all three species in such a community, whereas diversity is lost when ecological processes occur over larger scales. Here, we test these predictions empirically using a non-transitive model community containing three populations of Escherichia coli. We find that diversity is rapidly lost in our experimental community when dispersal and interaction occur over relatively large spatial scales, whereas all populations coexist when ecological processes are localized.     

Peat record reflecting Holocene climatic change in the Zoigê Plateau and AMS radiocarbon dating

Through the use of reliable AMS dating of high resolution (15–30 years) peat and the establishment of monsoon climate proxies sequence, we have been able to recognize several cold, dry events in the Tibetan Plateau during the Holocene. The more obvious ones occurred around 12800, 11300, 10200, 9580, 8900, 6400, 4400, 3700, 2800 and 1500 cal. aBP. These events correlate well with both ice rafting events recorded in high latitude North Atlantic Ocean sediment cores and cooling events in the low latitude SST. Spectral analysis indicates high frequency climate variation on centennial-millennial time scale during the Holocene. This further reflects Holocene climate instability and the existence of centennial-millenium scale rhythm in mid latitude areas as well.     

Polyisoprenyl phosphates: natural antiinflammatory lipid signals

Lipoxins (LX) and aspirin-triggered 15-epimer LX are leukocyte-derived eicosanoids generated during host defense that serve as down-regulatory signals. The specific intracellular events that govern cellular responses to inhibitory extracellular signals are of wide interest in order to understand pivotal intracellular events in diseases characterized by enhanced inflammatory responses, such as asthma, rheumatoid arthritis and atherosclerosis. We recently uncovered a novel role for polyisoprenyl phosphates, in particular presqualene diphosphate (PSDP), as natural down-regulatory signals in human neutrophils that directly inhibit phospholipase D and superoxide anion generation. Activation of LXA₄ receptors (ALXR) reverses proinflammatory receptor-initiated decrements in PSDP and inhibits cellular responses. These findings represent evidence for a novel paradigm for lipid-protein interactions in the control of cellular responses, namely receptor-initiated degradation of repressor lipids that is subject to regulation by aspirin treatment via the actions of aspirin-triggered 15-epimer LX at the ALXR, and identify new templates for antiinflammatory drugs by design.     

The functions of mucosal T cells in containing the indigenous commensal flora of the intestine

There is an immense load of non-pathogenic commensal bacteria in the distal small intestine and the colon of mammals. The physical barrier that prevents penetration (translocation) of these organisms into the body is a simple epithelium comprised of the single enterocyte/colonocyte cell layer with its overlying mucus. In this review, we discuss the roles of intestinal T cells in initiating and regulating innate and adaptive mucosal immune responses of the mucosal immune system that avoid or limit penetration of the commensal intestinal bacteria. Received 9 August 2002; accepted 9 September 2002 RID="*" ID="*"Corresponding author.