Annual rings in a native Hawaiian tree, Sophora chrysophylla, on Maunakea, Hawaiʻi

Annual rings are not commonly produced in tropical trees because they grow in a relatively aseasonal environment. However, in the subalpine zones of Hawaiʻi's highest volcanoes, there is often strong seasonal variability in temperature and rainfall. Using classical dendrochronological methods, annual growth rings were shown to occur in Sophora chrysophylla, a native tree species on Maunakea, Hawaiʻi. Chronologies were established from nearby non-native, live conifer trees and these were used to verify the dates from a total of 52 series from 22 S. chrysophylla trees, establishing an 86-y chronology (1926–2011). Ring-width patterns were significantly correlated with monthly rainfall from August of the previous year. This study is the first in the eastern tropical Pacific region to demonstrate annual growth rings in trees.postprin

Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH) is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH)-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI), 17β-hydroxysteroid dehydrogenase type III (17βHSD III), prostaglandin D (PGD)-synthetase and oestrogen sulphotransferase (EST)) is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH

Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells

Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases

A prickly problem: developing a volunteer-friendly tool for monitoring populations of a terrestrial urban mammal, the West European hedgehog (Erinaceus europaeus)

Across Europe, hedgehogs (Erinaceus europaeus) appear to be in decline in both urban and rural landscapes. Current methods used to monitor urban populations are, however, associated with several potential limitations. In this study, we conducted hedgehog footprint-tunnel surveys in 219 residential gardens across Reading, UK between May–September in 2013 and/or 2014; gardens were surveyed for five continuous days. Single-species occupancy models were used to investigate factors influencing hedgehog occupancy and two-species occupancy models were used to estimate a species interaction factor (SIF) between hedgehogs and (a) badgers (Meles meles), (b) foxes (Vulpes vulpes) and (c) dogs (Canis familiaris). The five-day survey protocol was associated with a false-absence error rate of 0.1–0.4%, indicating that it was a reliable method for determining hedgehog presence; conversely, 34.7% of householders were not able to correctly predict hedgehog presence or absence. Hedgehogs were widely distributed across Reading, but detected in only 32–40% of gardens. None of the within-garden or outside-garden factors investigated significantly affected hedgehog occupancy in the single-species models, but the two-species models indicated that badgers (SIF = 0.471 ± 0.188), but not foxes (SIF = 0.954 ± 0.048) or dogs (SIF = 0.780 ± 0.228), negatively affected the presence of hedgehogs in gardens, although not significantly. Overall, footprint-tunnels represent a viable field method for monitoring urban hedgehog populations, however, other approaches are required to identify factors that make gardens "hedgehog friendly"

Modelling Oscillator synchronisation during vertebrate axis segmentation

he somitogenesis clock regulates the periodicity with which somites form in the posterior pre-somitic mesoderm. Whilst cell heterogeneity results in noisy oscillation rates amongst constituent cells, synchrony within the population is maintained as oscillators are entrained via juxtracine signalling mechanisms. Here we consider a population of phase-coupled oscillators and investigate how biologically motivated perturbations to the entrained state can perturb synchrony within the population. We find that the ratio of mitosis length to clock period can influence levels of desynchronisation. Moreover, we observe that random cell movement, and hence change of local neighbourhoods, increases synchronisation

Independent predictors of failure up to 7.5 years after 35 386 single-brand cementless total hip replacements: a retrospective cohort study using National Joint Registry data

The popularity of cementless total hip replacement (THR) has surpassed cemented THR in England and Wales. This retrospective cohort study records survival time to revision following primary cementless THR with the most common combination (accounting for almost a third of all cementless THRs), and explores risk factors independently associated with failure, using data from the National Joint Registry for England and Wales. Patients with osteoarthritis who had a DePuy Corail/Pinnacle THR implanted between the establishment of the registry in 2003 and 31 December 2010 were included within analyses. There were 35 386 procedures. Cox proportional hazard models were used to analyse the extent to which the risk of revision was related to patient, surgeon and implant covariates. The overall rate of revision at five years was 2.4% (99% confidence interval 2.02 to 2.79). In the final adjusted model, we found that the risk of revision was significantly higher in patients receiving metal-on-metal (MoM: hazard ratio (HR) 1.93, p < 0.001) and ceramic-on-ceramic bearings (CoC: HR 1.55, p = 0.003) compared with the best performing bearing (metal-on-polyethylene). The risk of revision was also greater for smaller femoral stems (sizes 8 to 10: HR 1.82, p < 0.001) compared with mid-range sizes. In a secondary analysis of only patients where body mass index (BMI) data were available (n = 17 166), BMI ≥ 30 kg/m2 significantly increased the risk of revision (HR 1.55, p = 0.002). The influence of the bearing on the risk of revision remained significant (MoM: HR 2.19, p < 0.001; CoC: HR 2.09, p = 0.001). The risk of revision was independent of age, gender, head size and offset, shell, liner and stem type, and surgeon characteristics. We found significant differences in failure between bearing surfaces and femoral stem size after adjustment for a range of covariates in a large cohort of single-brand cementless THRs. In this study of procedures performed since 2003, hard bearings had significantly higher rates of revision, but we found no evidence that head size had an effect. Patient characteristics, such as BMI and American Society of Anesthesiologists grade, also influence the survival of cementless components

Escape rate and Hausdorff measure for entire functions

The escaping set of an entire function is the set of points that tend to infinity under iteration. We consider subsets of the escaping set defined in terms of escape rates and obtain upper and lower bounds for the Hausdorff measure of these sets with respect to certain gauge functions.Comment: 24 pages; some errors corrected, proof of Theorem 2 shortene

Hyperbolic entire functions and the Eremenko–Lyubich class: Class B or not class B?

Hyperbolicity plays an important role in the study of dynamical systems, and is a key concept in the iteration of rational functions of one complex variable. Hyperbolic systems have also been considered in the study of transcendental entire functions. There does not appear to be an agreed definition of the concept in this context, due to complications arising from the non-compactness of the phase space. In this article, we consider a natural definition of hyperbolicity that requires expanding properties on the preimage of a punctured neighbourhood of the isolated singularity. We show that this definition is equivalent to another commonly used one: a transcendental entire function is hyperbolic if and only if its postsingular set is a compact subset of the Fatou set. This leads us to propose that this notion should be used as the general definition of hyperbolicity in the context of entire functions, and, in particular, that speaking about hyperbolicity makes sense only within the Eremenko–Lyubich classB of transcendental entire functions with a bounded set of singular values. We also considerably strengthen a recent characterisation of the class B, by showing that functions outside of this class cannot be expanding with respect to a metric whose density decays at most polynomially. In particular, this implies that no transcendental entire function can be expanding with respect to the spherical metric. Finally we give a characterisation of an analogous class of functions analytic in a hyperbolic domain

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use