Systematics and Biogeography of Hard Ticks, a Total Evidence Approach

Systematic relationships among the basal Ixodidae are examined using one morphological and three molecular data sets, 18S and 28S nuclear and 16S mitochondrial rDNA. Although different combinations of partitions are incompatible in a partition homogeneity test, combining them produces similar or better support for most major lineages through both additive and complementary effects. The different data sets are not complete for all taxa, but inclusion or exclusion of taxa with missing data for one or more data sets (8 of 29 ingroup taxa) does not influence overall tree topology and only weakly affects support levels. The only notable effect was based on gap treatment in the 28S data set. Gap treatment completely changes the arrangement and support levels for one basal node. The combined analyses show strong support for the Metastriata, a lineage including most endemic Australian Ixodes , and a lineage including the remaining Ixodes , but not for the Prostriata (= Ixodes s.l.). The distribution pattern of endemic Australian taxa (nearly all included in three exclusively Australian basal lineages) suggests that these lineages, and by extension the Ixodidae, originated after the isolation of Australia in the late Cretaceous, much more recently than previously indicated.     

A FORTRAN program for the calculation and analysis of two-locus linkage disequilibrium coefficients

Summary A FORTRAN program was written that calculates composite linkage disequilibrium coefficients from genotypic data. Chi-square tests determine whether coefficients calculated for allele and locus pairs are significantly greater than zero. A subroutine is provided that partitions the variance in linkage disequilibrium into within- and between-subpopulation components. Output obtained from analysis of allozyme data collected from natural subpopulations of the house fly (Musca domestica L.) are included to illustrate features of the program.Journal Paper No. J-11345 of the Iowa Agriculture and Home Economics Experiment Station, Ames, Iowa. Project No. 2411     

30-Year Trends in Stroke Rates and Outcome in Auckland,New Zealand (1981-2012): A Multi-Ethnic Population-Based Series of Studies

Background

Insufficient data exist on population-based trends in morbidity and mortality to determine the success of prevention strategies and improvements in health care delivery in stroke. The aim of this study was to determine trends in incidence and outcome (1-year mortality, 28-day case-fatality) in relation to management and risk factors for stroke in the multi-ethnic population of Auckland, New Zealand (NZ) over 30-years.

Methods

Four stroke incidence population-based register studies were undertaken in adult residents (aged ≥15 years) of Auckland NZ in 1981–1982, 1991–1992, 2002–2003 and 2011–2012. All used standard World Health Organization (WHO) diagnostic criteria and multiple overlapping sources of case-ascertainment for hospitalised and non-hospitalised, fatal and non-fatal, new stroke events. Ethnicity was consistently self-identified into four major groups. Crude and age-adjusted (WHO world population standard) annual incidence and mortality with corresponding 95% confidence intervals (CI) were calculated per 100,000 people, assuming a Poisson distribution.

Results

5400 new stroke patients were registered in four 12 month recruitment phases over the 30-year study period; 79% were NZ/European, 6% Māori, 8% Pacific people, and 7% were of Asian or other origin. Overall stroke incidence and 1-year mortality decreased by 23% (95% CI 5%-31%) and 62% (95% CI 36%-86%), respectively, from 1981 to 2012. Whilst stroke incidence and mortality declined across all groups in NZ from 1991, Māori and Pacific groups had the slowest rate of decline and continue to experience stroke at a significantly younger age (mean ages 60 and 62 years, respectively) compared with NZ/Europeans (mean age 75 years). There was also a decline in 28-day stroke case fatality (overall by 14%, 95% CI 11%-17%) across all ethnic groups from 1981 to 2012. However, there were significant increases in the frequencies of pre-morbid hypertension, myocardial infarction, and diabetes mellitus, but a reduction in frequency of current smoking among stroke patients.

Conclusions

In this unique temporal series of studies spanning 30 years, stroke incidence, early case-fatality and 1-year mortality have declined, but ethnic disparities in risk and outcome for stroke persisted suggesting that primary stroke prevention remains crucial to reducing the burden of this disease.     

Perioperative Intravenous Acetaminophen Attenuates Lipid Peroxidation in Adults Undergoing Cardiopulmonary Bypass: A Randomized Clinical Trial

BackgroundCardiopulmonary bypass (CPB) lyses erythrocytes and induces lipid peroxidation, indicated by increasing plasma concentrations of free hemoglobin, F₂-isoprostanes, and isofurans. Acetaminophen attenuates hemeprotein-mediated lipid peroxidation, reduces plasma and urine concentrations of F₂-isoprostanes, and preserves kidney function in an animal model of rhabdomyolysis. Acetaminophen also attenuates plasma concentrations of isofurans in children undergoing CPB. The effect of acetaminophen on lipid peroxidation in adults has not been studied. This was a pilot study designed to test the hypothesis that acetaminophen attenuates lipid peroxidation in adults undergoing CPB and to generate data for a clinical trial aimed to reduce acute kidney injury following cardiac surgery.ConclusionsIntravenous acetaminophen attenuates the increase in intraoperative plasma isofuran concentrations that occurs during CPB, while urinary markers were unaffected.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01366976","term_id":"NCT01366976"}}NCT01366976     

Behavioral Immunity Suppresses an Epizootic in Caribbean Spiny Lobsters

Sociality has evolved in a wide range of animal taxa but infectious diseases spread rapidly in populations of aggregated individuals, potentially negating the advantages of their social interactions. To disengage from the coevolutionary struggle with pathogens, some hosts have evolved various forms of “behavioral immunity”; yet, the effectiveness of such behaviors in controlling epizootics in the wild is untested. Here we show how one form of behavioral immunity (i.e., the aversion of diseased conspecifics) practiced by Caribbean spiny lobsters (Panulirus argus) when subject to the socially transmitted PaV1 virus, appears to have prevented an epizootic over a large seascape. We capitalized on a "natural experiment" in which a die-off of sponges in the Florida Keys (USA) resulted in a loss of shelters for juvenile lobsters over a ~2500km² region. Lobsters were thus concentrated in the few remaining shelters, presumably increasing their exposure to the contagious virus. Despite this spatial reorganization of the population, viral prevalence in lobsters remained unchanged after the sponge die-off and for years thereafter. A field experiment in which we introduced either a healthy or PaV1-infected lobster into lobster aggregations in natural dens confirmed that spiny lobsters practice behavioral immunity. Healthy lobsters vacated dens occupied by PaV1-infected lobsters despite the scarcity of alternative shelters and the higher risk of predation they faced when searching for a new den. Simulations from a spatially-explicit, individual-based model confirmed our empirical results, demonstrating the efficacy of behavioral immunity in preventing epizootics in this system.     

C-Kit Promotes Growth and Migration of Human Cardiac Progenitor Cells via the PI3K-AKT and MEK-ERK Pathways

A recent phase I clinical trial (SCIPIO) has shown that autologous c-kit+ cardiac progenitor cells (CPCs) improve cardiac function and quality of life when transplanted into patients with ischemic heart disease. Although c-kit is widely used as a marker of resident CPCs, its role in the regulation of the cellular characteristics of CPCs remains unknown. We hypothesized that c-kit plays a role in the survival, growth, and migration of CPCs. To test this hypothesis, human CPCs were grown under stress conditions in the presence or absence of SCF, and the effects of SCF-mediated activation of c-kit on CPC survival/growth and migration were measured. SCF treatment led to a significant increase in cell survival and a reduction in cell death under serum depletion conditions. In addition, SCF significantly promoted CPC migration in vitro. Furthermore, the pro-survival and pro-migratory effects of SCF were augmented by c-kit overexpression and abrogated by c-kit inhibition with imatinib. Mechanistically, c-kit activation in CPCs led to activation of the PI3K and the MAPK pathways. With the use of specific inhibitors, we confirmed that the SCF/c-kit-dependent survival and chemotaxis of CPCs are dependent on both pathways. Taken together, our findings suggest that c-kit promotes the survival/growth and migration of human CPCs cultured ex vivo via the activation of PI3K and MAPK pathways. These results imply that the efficiency of CPC homing to the injury site as well as their survival after transplantation may be improved by modulating the activity of c-kit.     

Dicer Regulates Differentiation and Viability during Mouse Pancreatic Cancer Initiation

miRNA levels are altered in pancreatic ductal adenocarcinoma (PDA), the most common and lethal pancreatic malignancy, and intact miRNA processing is essential for lineage specification during pancreatic development. However, the role of miRNA processing in PDA has not been explored. Here we study the role of miRNA biogenesis in PDA development by deleting the miRNA processing enzyme Dicer in a PDA mouse model driven by oncogenic Kras. We find that loss of Dicer accelerates Kras driven acinar dedifferentiation and acinar to ductal metaplasia (ADM), a process that has been shown to precede and promote the specification of PDA precursors. However, unconstrained ADM also displays high levels of apoptosis. Dicer loss does not accelerate development of Kras driven PDA precursors or PDA, but surprisingly, we observe that mouse PDA can develop without Dicer, although at the expense of proliferative capacity. Our data suggest that intact miRNA processing is involved in both constraining pro-tumorigenic changes in pancreatic differentiation as well as maintaining viability during PDA initiation.     

Dynamics of nutrient uptake strategies: lessons from the tortoise and the hare

Many autotrophs vary their allocation to nutrient uptake in response to environmental cues, yet the dynamics of this plasticity are largely unknown. Plasticity dynamics affect the extent of single versus multiple nutrient limitation and thus have implications for plant ecology and biogeochemical cycling. Here we use a model of two essential nutrients cycling through autotrophs and the environment to determine conditions under which different plastic or fixed nutrient uptake strategies are adaptive. Our model includes environment-independent costs of being plastic, environment-dependent costs proportional to the rate of plastic change, and costs of being mismatched to the environment, the last of which is experienced by both fixed and plastic types. In equilibrium environments, environment-independent costs of being plastic select for tortoise strategies—fixed or less plastic types—provided that they are sufficiently close to co-limitation. At intermediate levels of environmental fluctuation forced by periodic nutrient inputs, more hare-like plastic strategies prevail because they remain near co-limitation. However, the fastest is not necessarily the best. The most adaptive strategy is an intermediate level of plasticity that keeps pace with environmental fluctuations, but is not faster. At high levels of environmental fluctuation, the environment-dependent cost of changing rapidly to keep pace with the environment becomes prohibitive and tortoise strategies again dominate. The existence and location of these thresholds depend on plasticity costs and rate, which are largely unknown empirically. These results suggest that the expectations for single nutrient limitation versus co-limitation and therefore biogeochemical cycling and autotroph community dynamics depend on environmental heterogeneity and plasticity costs.