A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology.

The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary optic neuropathy (LHON). The risk of developing the optic neuropathy shows strict maternal inheritance, and the ophthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences.     

Improving the Use of Species Distribution Models in Conservation Planning and Management under Climate Change

Choice of variables, climate models and emissions scenarios all influence the results of species distribution models under future climatic conditions. However, an overview of applied studies suggests that the uncertainty associated with these factors is not always appropriately incorporated or even considered. We examine the effects of choice of variables, climate models and emissions scenarios can have on future species distribution models using two endangered species: one a short-lived invertebrate species (Ptunarra Brown Butterfly), and the other a long-lived paleo-endemic tree species (King Billy Pine). We show the range in projected distributions that result from different variable selection, climate models and emissions scenarios. The extent to which results are affected by these choices depends on the characteristics of the species modelled, but they all have the potential to substantially alter conclusions about the impacts of climate change. We discuss implications for conservation planning and management, and provide recommendations to conservation practitioners on variable selection and accommodating uncertainty when using future climate projections in species distribution models.     

Site vegetation characteristics are more important than landscape context in determining bird assemblages in revegetation

The effectiveness of revegetation in providing habitat for fauna is expected to be determined both by within‐site factors and attributes of the landscape in which a revegetation site occurs. Most studies of fauna in revegetation have been conducted in landscapes that have been extensively cleared, modified or fragmented, and in Australia, predominantly in the southern temperate zone. We investigated how within‐site vegetation attributes and landscape context attributes were related to bird species richness and composition in a chronosequence of post‐mining rehabilitation sites within an otherwise intact landscape in tropical northern Australia. Our working hypothesis was that bird species richness in rehabilitating sites would be positively related to site vegetation structure and landscape context including (1) proximity to woodland and (2) the proportion of woodland within a 500‐m buffer of rehabilitation sites. Within each of 67 sites, we sampled vegetation once and surveyed for birds eight times over 16 months. Landscape context variables were calculated using GIS. There were large differences between bird assemblages of woodland and rehabilitation sites and between age classes of rehabilitation. Bird assemblages were strongly related to site vegetation attributes across all rehabilitation sites. Proximity to woodland was only related to bird assemblages in rehabilitation sites older than 4 years old. We conclude that the relative importance of landscape context and site variables at any point in time will be a function of how closely vegetation within the revegetation site matches the habitat resource requirements of individual species.     

A Small Novel A-Kinase Anchoring Protein (AKAP) That Localizes Specifically Protein Kinase A-Regulatory Subunit I (PKA-RI) to the Plasma Membrane

Protein kinase A-anchoring proteins (AKAPs) provide spatio-temporal specificity for the omnipotent cAMP-dependent protein kinase (PKA) via high affinity interactions with PKA regulatory subunits (PKA-RI, RII). Many PKA-RII-AKAP complexes are heavily tethered to cellular substructures, whereas PKA-RI-AKAP complexes have remained largely undiscovered. Here, using a cAMP affinity-based chemical proteomics strategy in human heart and platelets, we uncovered a novel, ubiquitously expressed AKAP, termed small membrane (sm)AKAP due to its specific localization at the plasma membrane via potential myristoylation/palmitoylation anchors. In vitro binding studies revealed specificity of smAKAP for PKA-RI (K_d = 7 nm) over PKA-RII (K_d = 53 nm) subunits, co-expression of smAKAP with the four PKA R subunits revealed an even more exclusive specificity of smAKAP for PKA-RIα/β in the cellular context. Applying the singlet oxygen-generating electron microscopy probe miniSOG indicated that smAKAP is tethered to the plasma membrane and is particularly dense at cell-cell junctions and within filopodia. Our preliminary functional characterization of smAKAP provides evidence that, like PKA-RII, PKA-RI can be tightly tethered by a novel repertoire of AKAPs, providing a new perspective on spatio-temporal control of cAMP signaling.     

The Coronatine Toxin of Pseudomonas syringae Is a Multifunctional Suppressor of Arabidopsis Defense

The phytotoxin coronatine (COR) promotes various aspects of Pseudomonas syringae virulence, including invasion through stomata, growth in the apoplast, and induction of disease symptoms. COR is a structural mimic of active jasmonic acid (JA) conjugates. Known activities of COR are mediated through its binding to the F-box–containing JA coreceptor CORONATINE INSENSITIVE1. By analyzing the interaction of P. syringae mutants with Arabidopsis thaliana mutants, we demonstrate that, in the apoplastic space of Arabidopsis, COR is a multifunctional defense suppressor. COR and the critical P. syringae type III effector HopM1 target distinct signaling steps to suppress callose deposition. In addition to its well-documented ability to suppress salicylic acid (SA) signaling, COR suppresses an SA-independent pathway contributing to callose deposition by reducing accumulation of an indole glucosinolate upstream of the activity of the PEN2 myrosinase. COR also suppresses callose deposition and promotes bacterial growth in coi1 mutant plants, indicating that COR may have multiple targets inside plant cells.     

High frequency spikes in long period blood cell oscillations

Several hematological diseases are characterised by oscillations of various blood cell populations. Two of these are a variant of chronic myelogenous leukemia (CML) and cyclical neutropenia (CN). These oscillations typically have long periods ranging from 20 to 60 days, despite the fact that the stem cell cycling time is thought to be of the order of 2–3 days. Clinical data from humans and laboratory data from the grey collie animal model of CN is suggestive of the idea that these long period oscillations may also contain higher frequency spiky oscillations. We show how such oscillations can be understood in the context of slow periodic stem cell oscillations, by analysing a two component differential-delay equation model of stem cell and neutrophil populations.For Karl Hadeler, on his 70th birthday, leader, teacher, colleague and friend.