Towards an interactive,process‐based approach to understanding range shifts: developmental and environmental dependencies matter

Many species are undergoing distributional shifts in response to climate change. However, wide variability in range shifting rates has been observed across taxa, and even among closely‐related species. Attempts to link climate‐mediated range shifts to traits has often produced weak or conflicting results. Here we investigate interactive effects of developmental processes and environmental stress on the expression of traits relevant to range shifts. We use an individual‐based modelling approach to assess how different developmental strategies affect range shift rates under a range of environmental conditions. We find that under stressful conditions, such as at the margins of the species’ fundamental niche, investment in prolonged development leads to the greatest rates of range shifting, especially when longer time in development leads to improved fecundity and dispersal‐related traits. However, under benign conditions, and when traits are less developmentally plastic, shorter development times are preferred for rapid range shifts, because higher generational frequency increases the number of individual dispersal events occurring over time. Our results suggest that the ability of a species to range shift depends not only on their dispersal and colonisation characteristics but also how these characteristics interact with developmental strategies. Benefits of any trait always depended on the environmental and developmental sensitivity of life history trait combinations, and the environmental conditions under which the range shift takes place. Without considering environmental and developmental sources of variation in the expression of traits relevant to range shifts, there is little hope of developing a general understanding of intrinsic drivers of range shift potential.     

Minimizing the biodiversity impact of Neotropical oil palm development

Oil palm agriculture is rapidly expanding in the Neotropics, at the expense of a range of natural and seminatural habitats. A key question is how this expansion should be managed to reduce negative impacts on biodiversity. Focusing on the Llanos of Colombia, a mixed grassland–forest system identified as a priority zone for future oil palm development, we survey communities of ants, dung beetles, birds and herpetofauna occurring in oil palm plantations and the other principal form of agriculture in the region – improved cattle pasture – together with those of surrounding natural forests. We show that oil palm plantations have similar or higher species richness across all four taxonomic groups than improved pasture. For dung beetles, species richness in oil palm was equal to that of forest, whereas the other three taxa had highest species richness in forests. Hierarchical modelling of species occupancy probabilities indicated that oil palm plantations supported a higher proportion of species characteristic of forests than did cattle pastures. Across the bird community, occupancy probabilities within oil palm were positively influenced by increasing forest cover in a surrounding 250 m radius, whereas surrounding forest cover did not strongly influence the occurrence of other taxonomic groups in oil palm. Overall, our results suggest that the conversion of existing improved pastures to oil palm has limited negative impacts on biodiversity. As such, existing cattle pastures of the Colombian Llanos could offer a key opportunity to meet governmental targets for oil palm development without incurring significant biodiversity costs. Our results also highlight the value of preserving remnant forests within these agricultural landscapes, protecting high biodiversity and exporting avian ‘spill‐over’ effects into oil palm plantations.     

Expression of the TEL-Syk Fusion Protein in Hematopoietic Stem Cells Leads to Rapidly Fatal Myelofibrosis in Mice

The TEL-Syk fusion protein was isolated from a patient with myelodysplasia with megakaryocyte blasts. Expression of TEL-Syk transforms interleukin-3 (IL-3)-dependent Ba/F3 cells in vitro by deregulating STAT5-mediated signal transduction pathways. In vivo, TEL-Syk expression in pre-B cells blocks B cell differentiation, leading to lymphoid leukemia. Here, we demonstrate that TEL-Syk introduced into fetal liver hematopoietic cells, which are then adoptively transferred into lethally irradiated recipients, leads to an aggressive myelodysplasia with myelofibrosis that is lethal in mice by 60–75 days. Expression of TEL-Syk induces a short-lived myeloexpansion that is rapidly followed by bone marrow failure and extreme splenic/hepatic fibrosis accompanied by extensive apoptosis. The disease is dependent on Syk kinase activity. Analysis of serum from TEL-Syk mice reveals an inflammatory cytokine signature reminiscent of that found in the sera from patients and mouse models of myeloproliferative neoplasms. TEL-Syk expressing cells showed constitutive STAT5 phosphorylation, which was resistant to JAK inhibition, consistent with deregulated cytokine signaling. These data indicate that expression of TEL-Syk in fetal liver hematopoietic cells results in JAK-independent STAT5 phosphorylation ultimately leading to a uniquely aggressive and lethal form of myelofibrosis.     

The structure of F1-ATPase from Saccharomyces cerevisiae inhibited by its regulatory protein IF1

The structure of F₁-ATPase from Saccharomyces cerevisiae inhibited by the yeast IF₁ has been determined at 2.5 Å resolution. The inhibitory region of IF₁ from residues 1 to 36 is entrapped between the C-terminal domains of the α_DP- and β_DP-subunits in one of the three catalytic interfaces of the enzyme. Although the structure of the inhibited complex is similar to that of the bovine-inhibited complex, there are significant differences between the structures of the inhibitors and their detailed interactions with F₁-ATPase. However, the most significant difference is in the nucleotide occupancy of the catalytic β_E-subunits. The nucleotide binding site in β_E-subunit in the yeast complex contains an ADP molecule without an accompanying magnesium ion, whereas it is unoccupied in the bovine complex. Thus, the structure provides further evidence of sequential product release, with the phosphate and the magnesium ion released before the ADP molecule.     

Differences in kainate receptor involvement in hippocampal mossy fibre long-term potentiation depending on slice orientation

Long-term potentiation (LTP) is a well-established experimental model used to investigate the synaptic basis of learning and memory. LTP at mossy fibre - CA3 synapses in the hippocampus is unusual because it is normally N-methyl-d-aspartate (NMDA) receptor-independent. Instead it seems that the trigger for mossy fibre LTP involves kainate receptors (KARs). Although it is generally accepted that pre-synaptic KARs play an essential role in frequency facilitation and LTP, their subunit composition remains a matter of significant controversy. We have reported previously that both frequency facilitation and LTP can be blocked by selective antagonism of GluK1 (formerly GluR5/Glu(K5))-containing KARs, but other groups have failed to reproduce this effect. Moreover, data from receptor knockout and mRNA expression studies argue against a major role of GluK1, supporting a more central role for GluK2 (formerly GluR6/Glu(K6)). A potential reason underlying the controversy in the pharmacological experiments may reside in differences in the preparations used. Here we show differences in pharmacological sensitivity of synaptic plasticity at mossy fibre - CA3 synapses depend critically on slice orientation. In transverse slices, LTP of fEPSPs was invariably resistant to GluK1-selective antagonists whereas in parasagittal slices LTP was consistently blocked by GluK1-selective antagonists. In addition, there were pronounced differences in the magnitude of frequency facilitation and the sensitivity to the mGlu2/3 receptor agonist DCG-IV. Using anterograde labelling of granule cells we show that slices of both orientations possess intact mossy fibres and both large and small presynaptic boutons. Transverse slices have denser fibre tracts but a smaller proportion of giant mossy fibre boutons. These results further demonstrate a considerable heterogeneity in the functional properties of the mossy fibre projection.     

Genetic variation in cell death genes and risk of non-Hodgkin lymphoma

Background

Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5^th highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility.

Materials and Methods

We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate.

Results

Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63–4.82]; p_F = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing.

Conclusions

This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma.     

Coral reef recovery dynamics in a changing world

Coral reef ecosystems are degrading through multiple disturbances that are becoming more frequent and severe. The complexities of this degradation have been studied in detail, but little work has assessed characteristics that allow reefs to bounce back and recover between pulse disturbance events. We quantitatively review recovery rates of coral cover from pulse disturbance events among 48 different reef locations, testing the relative roles of disturbance characteristics, reef characteristics, connectivity and anthropogenic influences. Reefs in the western Pacific Ocean had the fastest recovery, whereas reefs in the geographically isolated eastern Pacific Ocean were slowest to recover, reflecting regional differences in coral composition, fish functional diversity and geographic isolation. Disturbances that opened up large areas of benthic space recovered quickly, potentially because of nonlinear recovery where recruitment rates were high. The type of disturbance had a limited effect on subsequent rates of reef recovery, although recovery was faster following crown-of-thorns starfish outbreaks. This inconsequential role of disturbance type may be in part due to the role of unaltered structural complexity in maintaining key reef processes, such as recruitment and herbivory. Few studies explicitly recorded potential ecological determinants of recovery, such as recruitment rates, structural complexity of habitat and the functional composition of reef-associated fish. There was some evidence of slower recovery rates within protected areas compared with other management systems and fished areas, which may reflect the higher initial coral cover in protected areas rather than reflecting a management effect. A better understanding of the driving role of processes, structural complexity and diversity on recovery may enable more appropriate management actions that support coral-dominated ecosystems in our changing climate.     

Role of vinculin in regulating focal adhesion turnover

Although vinculin (-/-) mouse embryo fibroblasts assemble focal adhesions (FAs), they spread more slowly, less extensively, and close a wound more rapidly than vinculin (+/+) cells. To investigate the structure and dynamics of FAs in these cells, we used real-time interference reflection microscopy (IRM) thus avoiding the need to express exogenous GFP-tagged FA proteins which may be misregulated. This showed that the FAs were smaller, less abundant and turned over more rapidly in vinculin null compared to wild-type cells. Expression of vinculin rescued the spreading defect and resulted in larger and more stable FAs. Phosphatidylinositol 4,5-bisphosphate (PIP2) is thought to play a role in vinculin activation by relieving an intramolecular association between the vinculin head (Vh) and tail (Vt) that masks the ligand binding sites in Vh and Vt. To investigate the role of the vinculin/PIP2 interaction in FA dynamics, we used a vinculin mutant lacking the C-terminal arm (residues 1053-1066) and referred to as the deltaC mutation. This mutation reduced PIP2 binding to a Vt deltaC polypeptide by >90% compared to wild type without affecting binding to Vh or F-actin. Interestingly, cells expressing the vinculin deltaC mutant assembled remarkably stable FAs. The results suggest that vinculin inhibits cell migration by stabilising FAs, and that binding of inositol phospholipids to Vt plays an important role in FA turnover.     

LTP inhibits LTD in the hippocampus via regulation of GSK3beta

Glycogen synthase kinase-3 (GSK3) has been implicated in major neurological disorders, but its role in normal neuronal function is largely unknown. Here we show that GSK3beta mediates an interaction between two major forms of synaptic plasticity in the brain, N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and NMDA receptor-dependent long-term depression (LTD). In rat hippocampal slices, GSK3beta inhibitors block the induction of LTD. Furthermore, the activity of GSK3beta is enhanced during LTD via activation of PP1. Conversely, following the induction of LTP, there is inhibition of GSK3beta activity. This regulation of GSK3beta during LTP involves activation of NMDA receptors and the PI3K-Akt pathway and disrupts the ability of synapses to undergo LTD for up to 1 hr. We conclude that the regulation of GSK3beta activity provides a powerful mechanism to preserve information encoded during LTP from erasure by subsequent LTD, perhaps thereby permitting the initial consolidation of learnt information.