New Zealand geckos (Diplodactylidae): Cryptic diversity in a post-Gondwanan lineage with trans-Tasman affinities

We used a multi-gene approach to assess the phylogenetic relationships of New Zealand diplodactylid geckos to their Australian and New Caledonian relatives and to one another. Data from nuclear (RAG-1, PDC) and mitochondrial (ND2, 16S) genes from >180 specimens representing all 19 recognized New Zealand taxa and all but two of 20 putatively new species suggested by previous studies were analyzed using Maximum Parsimony, Maximum Likelihood and Bayesian inference. All analyses retrieved a monophyletic New Zealand clade, most closely related to the Australian Diplodactylidae exclusive of Pseudothecadactylus. Hoplodactylus is paraphyletic and composed of two morphological groups: a broad-toed clade, consisting of the island-restricted, largest extant species, Hoplodactylus duvaucelii, and the species-rich, wide-ranging Hoplodactylus maculatus clade; and a narrow-toed clade, comprising five monophyletic subgroups: Naultinus, the Hoplodactylus pacificus and Hoplodactylus granulatus clades, and the distinctive species Hoplodactylus rakiurae and Hoplodactylus stephensi. Each of these lineages is here recognized at the generic level. Our data support recognition of 16 new species (36 total), and five new or resurrected genera (seven total). The New Zealand diplodactylid radiation split from its Australian relatives 40.2mya (95% highest posterior density estimate 28.9-53.5), after the opening of the Tasman Sea. Their distribution cannot, therefore, be regarded as derived as a result of Gondwanana vicariance. The age of the New Zealand crown group, 24.4mya (95% highest posterior density estimate 15.5-33.8), encompasses the period of the 'Oligocene drowning' of New Zealand and is consistent with the hypothesis that New Zealand was not completely inundated during this period. Major lineages within New Zealand geckos diverged chiefly during the mid- to late Miocene, probably in association with a suite of geological and climatological factors that have characterized the region's complex history.     

Total lactate dehydrogenase activity of tail muscle is not cold-adapted in nocturnal lizards from cool-temperate habitats

The dependence of metabolic processes on temperature constrains the behavior, physiology and ecology of many ectothermic animals. The evolution of nocturnality in lizards, especially in temperate regions, requires adaptations for activity at low temperatures when optimal body temperatures are unlikely to be obtained. We examined whether nocturnal lizards have cold-adapted lactate dehydrogenase (LDH). LDH was chosen as a representative metabolic enzyme. We measured LDH activity of tail muscle in six lizard species (n = 123: three nocturnal, two diurnal and one crepuscular) between 5 and 35 °C and found no differences in LDH-specific activity or thermal sensitivity among the species. Similarly, the specific activity and thermal sensitivity of LDH were similar between skinks and geckos. Similar enzyme activities among nocturnal and diurnal lizards indicate that there is no selection of temperature specific LDH enzyme activity at any temperature. As many nocturnal lizards actively thermoregulate during the day, LDH may be adapted for a broad range of temperatures rather than adapted specifically for the low temperatures encountered when the animals are active. The total activity of LDH in tropical and temperate lizards is not cold-adapted. More data are required on biochemical adaptations and whole animal thermal preferences before trends can be established.     

Thematic review series: The immune system and atherogenesis. Cytokine regulation of macrophage functions in atherogenesis

This review will focus on the role of cytokines in the behavior of macrophages, a prominent cell type of atherosclerotic lesions. Once these macrophages have immigrated into the vessel wall, they propagate the development of atherosclerosis by modifying lipoproteins, accumulating intracellular lipids, remodeling the extracellular environment, and promoting local coagulation. The numerous cytokines that have been detected in atherosclerosis, combined with the expression of large numbers of cytokine receptors on macrophages, are consistent with this axis being an important contributor to lesion development. Given the vast literature on cytokine-macrophage interactions, this review will be selective, with an emphasis on the major cytokines that have been detected in atherosclerotic lesions and their effects on properties that are relevant to lesion formation and maturation. There will be an emphasis on the role of cytokines in regulating lipid metabolism by macrophages. We will provide an overview of the major findings in cell culture and then put these in the context of in vivo studies.     

Cysteine-scanning mutagenesis and thiol modification of the Rickettsia prowazekii ATP/ADP translocase: evidence that transmembrane regions I and II, but not III, are structural components of the aqueous translocation channel

The contribution of transmembrane regions I, II, and III of the Rickettsia prowazekii ATP/ADP translocase to the structure of the putative water-filled ATP translocation channel was evaluated from the accessibility of hydrophilic, thiol-reactive, methanethiosulfonate reagents to a library of 68 independent cysteine-substitution mutants heterologously expressed in Escherichia coli. The MTS reagents used were MTSES (negatively charged) and MTSET and MTSEA (both positively charged). Mutants F036C, Y042C, and R046C (TM I), K066C and P072C (TM II), and F101C, F105C, F108C, Y113C, and P114C (TM III) had no assayable transport activity, indicating that cysteine substitution at these positions may not be tolerated. All three MTS reagents inhibit the transport of ATP in mutants of TM I (L039C, S043C, S047C, I048C) and TM II (S061C, S063C, T067C, I069C, V070C, A074C). Further, these residues appear to cluster along a single face of the transmembrane domain. Preexposure of MTS-reactive mutants S047C (TM I) and T067C (TM II) to high levels of ATP resulted in protection from MTS-mediated inhibition. This indicated that both TM I and TM II make major contributions to the structure of an aqueous ATP translocation pathway. Finally, on the basis of the lack of accessibility of charged MTS reagents to the thiol groups in mutants of TM III, it appears that TM III is not exposed to the ATP translocation channel. Cysteine substitution of residues constituting a highly conserved "phenylalanine face" in TM III resulted in ablation of ATP transport activity. Further, substituting these phenylalanine residues for either isoleucine or tyrosine also resulted in much lower transport activity, indicating that some property of phenylalanine at these positions that is not shared by cysteine, isoleucine, or tyrosine is critical to translocase activity.     

Comparative genomics of emerging human ehrlichiosis agents

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.     

Have the Harmful Effects of Introduced Rats on Islands been Exaggerated?

Introduced rats are now being eradicated from many islands. Increasingly, these eradications are contested by activists claiming moral, legal, cultural, historic or scientific reasons and poorly documented evidence of effects. We reviewed the global literature on the effects of rats on island flora and fauna. We then used New Zealand as a case study because of its four-decade history of rat eradications and many detailed and innovative studies of how rats affect native species. These include use of exclosures, local manipulations of rat populations, video surveillance, and measurements of responses following eradications. The most intensive studies have been on the Pacific rat (Rattus exulans), a small South-East Asian species spread by Polynesians throughout the Pacific. These and the more recently introduced Norway rat (R. norvegicus) and ship (roof) rat (R. rattus) suppress some forest plants, and are associated with extinctions or declines of flightless invertebrates, ground-dwelling reptiles, land birds, and burrowing seabirds. On islands off France, Norway rats are also implicated in declines of shrews. Globally, ship rats were associated with declines or extinctions of the largest number of indigenous vertebrate species (60), including small mammals such as deer mice and bats. Effects of rats on forest trees and seabird populations are sufficiently pervasive to affect ecosystem structure and function. However, the data are patchy. Deficiencies in our knowledge would be reduced by documenting distribution and abundance of indigenous species before and after eradications. Comprehensive measurements of the responses of indigenous species to rat eradications would enable the development of testable models of rat invasion effects.     

JColorGrid: software for the visualization of biological measurements

Background  

Two-dimensional data colourings are an effective medium by which to represent three-dimensional data in two dimensions. Such "color-grid" representations have found increasing use in the biological sciences (e.g. microarray 'heat maps' and bioactivity data) as they are particularly suited to complex data sets and offer an alternative to the graphical representations included in traditional statistical software packages. The effectiveness of color-grids lies in their graphical design, which introduces a standard for customizable data representation. Currently, software applications capable of generating limited color-grid representations can be found only in advanced statistical packages or custom programs (e.g. micro-array analysis tools), often associated with steep learning curves and requiring expert knowledge.     

Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice

Previous studies demonstrated that overexpression of angiotensinogen (AGT) in adipose tissue increased blood pressure. However, the contribution of endogenous AGT in adipocytes to the systemic renin-angiotensin system (RAS) and blood pressure control is undefined. To define a role of adipocyte-derived AGT, mice with loxP sites flanking exon 2 of the AGT gene (Agt(fl/fl)) were bred to transgenic mice expressing Cre recombinase under the control of an adipocyte fatty acid-binding protein 4 promoter (aP2) promoter to generate mice with adipocyte AGT deficiency (Agt(aP2)). AGT mRNA abundance in adipose tissue and AGT secretion from adipocytes were reduced markedly in adipose tissues of Agt(aP2) mice. To determine the contribution of adipocyte-derived AGT to the systemic RAS and blood pressure control, mice were fed normal laboratory diet for 2 or 12 mo. In males and females of each genotype, body weight and fat mass increased with age. However, there was no effect of adipocyte AGT deficiency on body weight, fat mass, or adipocyte size. At 2 and 12 mo of age, mice with deficiency of AGT in adipocytes had reduced plasma concentrations of AGT (by 24-28%) compared with controls. Moreover, mice lacking AGT in adipocytes exhibited reduced systolic blood pressures compared with controls (Agt(fl/fl), 117 ± 2; Agt(aP2), 110 ± 2 mmHg; P < 0.05). These results demonstrate that adipocyte-derived AGT contributes to the systemic RAS and blood pressure control.     

High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma

In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED), 3 times/week, 10-weeks). The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome), and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th), cytolytic (CTL), and regulatory (Treg) T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF) by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden), increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression), lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity), and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis). These results suggest that the deleterious effects of high trait anxiety could be: exacerbated by life-stressors, accentuated by the stress of cancer diagnosis/treatment, and mediate increased tumor progression and/or metastasis. Therefore, it may be beneficial to investigate the use of chemotherapy-compatible anxiolytic treatments immediately following cancer diagnosis, and during cancer treatment/survivorship.