bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrasting patterns of persistence and diversification in vicars of a widespread Australian lizard lineage (the Oedura marmorata complex)
Authors: Oliver Paul M. , Smith Katie L. , Laver Rebecca J. , Doughty Paul , Adams Mark
Published: July 2014

Aim

Lineages in many parts of the world have distributions that have been shaped by range contraction in the face of deteriorating climatic conditions through the Neogene. When such lineages now consist of widely spaced vicariant populations (vicars) they provide opportunities (1) to compare and contrast the timing and pattern of diversification within and between major geographical regions, and (2) to examine how differential interactions with geography, climate and localized adaptation may have shaped idiosyncratic patterns of genetic diversification.

Location

Australian Arid Zone (AAZ) and Australian Monsoonal Tropics (AMT).

Methods

We compiled and analysed mitochondrial DNA, nuclear DNA and allozyme datasets to determine the evolutionary history and genetic diversity of isolated populations of a gecko lineage (the Oedura marmorata complex and related taxa) distributed across the Australian monsoonal and arid biomes.

Results

Three widely allopatric lineages in the AAZ diverged during the late Miocene and Plio‐Pleistocene. Populations in the AMT display much greater genetic turnover than those in the AAZ over equivalent geographical distances, and also include several lineages that are of equal or greater age than all diversity in the AAZ. Saxicoline lineages tend to show higher genetic diversity and/or have more restricted ranges than arboreal relatives in both biomes.

Main conclusions

Lineages of Oedura show contrasting patterns of diversification in the two major biomes they inhabit. Diversity in the arid biome is younger and restricted to widely separated refugia, reflecting the younger age and pervasive harshness of this environment. Higher diversity in the AMT is also indicative of persistence, but at much finer geographical scales and broadly over a longer period of time, perhaps reflecting the more continuous spatial and temporal distribution of equitable habitats within this region. Finally, the wider distribution of arboreal lineages in both biomes suggests that ecological flexibility has also shaped the contrasting patterns of distribution in related lineages, and supports the contention that an association with rocks has shaped high lineage diversity in many taxa from the Australian Monsoonal Tropics.
Molecular and Morphometric Characteristics of Ceratomyxa hamour n. sp. (Myxosporea: Bivalvulida) Infecting the Gallbladder of the Orange‐spotted Grouper Epinephelus coioides from the Arabian Gulf, Saudi Arabia
Authors: Mansour Lamjed , Al‐Qahtani Hussain A. , Al‐Quraishy Saleh , Abdel‐Baki Abdel‐Azeem S.
Published: July 2014

Ceratomyxa hamour n. sp. was found to infect the gallbladder of the orange‐spotted grouper, Epinephelus coioides located off the Saudi Arabian coast of the Arabian Gulf. The infection was reported as a free‐floating spore in the bile, and pseudoplasmodia were not observed. Mature spores were crescent‐shaped and measured on average 7 μm in length and 16 μm in thickness. The polar capsule, meanwhile, had length to width measurements of 4 μm and 3 μm on average. A periodical survey was conducted throughout a sampling period between December 2012 and December 2013, with the results showing that the parasite was present throughout the year with a mean prevalence of 32.6%. The objective of this study was to characterize this new species based on its morphological and molecular differences from previously described species. Molecular analysis based on the partial sequence of the SSU rDNA gene, showed the highest similarity (97.8%) to Ceratomyxa buri, reported in the cultured yellow tail Seriola quinqueradiata in Japan. Indeed, C. buri and the new species described here formed an individual cluster with a high degree of bootstrap support. This is the first reported species of genus Ceratomyxa from the Arabian Gulf fishes off Saudi Arabia.
A detailed appraisal of mesocolic lymphangiology – an immunohistochemical and stereological analysis
Authors: Culligan Kevin , Sehgal Rishabh , Mulligan Daniel , Dunne Colum , Walsh Stewart , Quondamatteo Fabio , Dockery Peter , Coffey J. Calvin
Published: July 2014

Inadequate resection of the adjoining mesentery is associated with adverse outcome for colon cancer. Disruption of the integrity of the mesenteric lymphatic package has been implicated in this, though not proven. Recent studies have determined mesenteric anatomy and histology and now provide an opportunity to determine accurately the distribution of lymphatic vessels. The aim of this study was to characterise the distribution of the lymphatic vessels (LV) within the small intestinal and colonic mesentery, and in Toldt's fascia, which lies between the mesocolon and underlying retroperitoneum. Mesenteric samples were harvested from 12 human cadavers. Samples were taken from the small bowel mesentery, ascending, transverse, descending mesocolon and from both apposed and non‐apposed portions of the mesosigmoid. Serial sections were stained immunohistochemically with monoclonal antibody D2‐40 (podoplanin), and Masson's Trichrome. Lymphatic vessel (LV) density and radius of diffusion were determined using a stereological approach. A lymphatic network was embedded within the mesenteric connective tissue lattice throughout each mesenteric region. LV were identifiable within the submesothelial connective tissue where they measured 10.2 ± 4.1 μm in diameter and had an average radius of diffusion of 174.72 ± 97.68 μm. Unexpectedly, LV were identified in Toldt's fascia, where they measured 4.3 ± 3.1 μm in diameter and had a radius of diffusion of 165.12 ± 66.26 μm. This is the first study systematically to determine and quantify the distribution of lymphatic vessels within the mesenteric organ and to demonstrate the presence of such vessels within Toldt's fascia. A rich lymphatic network occupies all levels of the mesenteric connective tissue lattice. Within the latter, they are found within 0.1 mm of peritonealised mesenteric surfaces and are separated by an average distance of 0.17 mm and may be particularly vulnerable during surgery.
The Income Elasticity of Nonlife Insurance: A Reassessment
Authors: Millo Giovanni
Published: July 2014

In aggregate insurance regressions at the country level, the question whether insurance is a normal or superior good translates into whether income elasticity is significantly greater than one or not. Twenty‐five years after a seminal article, I reassess the income elasticity of nonlife insurance by means of homogeneous and heterogeneous versions of the common correlated effects estimator, controlling for common factors and individual trends and characterizing the average behavior of insurance markets while allowing for individual heterogeneity. The evidence supports the existence of a cointegrating behavior between insurance consumption and GDP and the view of nonlife insurance as a normal good.
OPERA: responses to peginterferon and ribavirin therapy in a subgroup of interferon‐naïve patients with HIV/HCV genotype 2/3 co‐infection in Italy
Authors: Bruno Raffaele , Cariti Giuseppe , Nasta Paola , Capetti Amedeo , Ravasio Veronica , Galli Massimo , Raise Enzo , Palmieri Giulio , Iannacone Claudio , Puoti Massimo
Published: July 2014

Background & Aims

Hepatitis C virus (HCV) genotype 3 (G3) is common among HIV/HCV co‐infected individuals and associated with moderate sustained virological response (SVR) rates with pegylated interferon (PEG‐IFN) plus ribavirin (RBV) therapy, while G2 is less frequent and associated with higher SVR. To determine SVR and other response rates, identify SVR predictors and analyse differences between G2 and G3 with PEG‐IFN/RBV in a large HIV/HCV G2/3 patient population.

Methods

This subgroup analysis of the prospective, observational OPERA (Optimized Pegylated interferon Efficacy and anti‐Retroviral Approach) study was conducted between 2005 and 2011 in Italy in PEG‐IFN/RBV‐naïve HIV/HCV patients. The primary efficacy endpoint was SVR rate (HCV RNA <50 IU/ml or undetectable 24 weeks after end‐of‐treatment).

Results

Five hundred and fifty‐six HCV G2/3 patients (G2 n = 60; G3 n = 496) were treated with PEG‐IFN alfa‐2a 180 μg/week or PEG‐IFN alfa‐2b 1.5 μg/kg, + RBV 13.6 ± 2.3 (mean ± SD) mg/kg/day for median 47 (26–54) weeks. SVR rates were 57.7%, 68.3% and 56.5% for G2/3, G2 and G3 respectively) and RVR rates were 53.2%, 57.1% and 45.8% respectively. Independent SVR predictors were undetectable baseline HIV RNA [adjusted odds ratio (AOR), 2.64; 95% CI: 1.523–4.565, P = 0.0005], age (AOR 0.95 per year; 95% CI: 0.908–0.994, P = 0.0258) and anti‐HCV treatment duration (AOR 1.034 per week; 95% CI: 1.013–1.057, P = 0.0019).

Conclusions

Undetectable HIV RNA, longer anti‐HCV treatment adherence and younger age were independent SVR predictors in treatment‐naïve HIV/HCV G2/3 patients receiving PEG‐IFN/RBV. Suppressing HIV RNA replication before anti‐HCV therapy and increasing adherence to PEG‐IFN/RBV treatment SVR rates may improve SVR.
Association of HLA‐DP/DQ, STAT4 and IL‐28B variants with HBV viral clearance in Tibetans and Uygurs in China
Authors: Liao Yun , Cai Bei , Li Yi , Chen Jie , Ying Binwu , Tao Chuanmin , Zhao Min , Ba Zhu , Zhang Zhaoxia , Wang Lanlan
Published: July 2014

Background & Aims

Several genome‐wide association studies have revealed that HLA‐DP/DQ, STAT4 and IL‐28B associated with liver diseases. But because of population heterogeneity, different races would have different causative polymorphisms. Therefore, in this study, we included Chinese Tibetans and Uygurs to examine the roles of these genes on HBV natural clearance.

Methods

A total of 1341 subjects including 908 Tibetans and 433 Uygurs were recruited. Seven single nucleotide polymorphisms (SNP) were genotyped.

Results

HLA‐DP/DQ polymorphisms associated with HBV natural clearance in both ethnicities (Tibetans, rs3077, OR = 0.61, 95% CI = 0.46–0.82; rs9277535, OR = 0.56, 95% CI = 0.41–0.75; rs7453920, OR = 0.64, 95%CI = 0.47–0.85; Uygurs, rs3077, OR = 0.48, 95% CI = 0.24–0.96; rs9277535, OR = 0.43, 95% CI = 0.20–0.91; rs7453920, OR = 0.62, 95% CI = 0.39–0.99), whereas no significant association was observed between IL‐28B with HBV natural clearance in neither ethnicities (P > 0.05). STAT4 rs7574865 seemed to be Tibetan specific in HBV natural clearance (OR = 0.76, 95% CI = 0.58–0.99). Moreover, in Tibetan patients, HLA‐DQ rs7453920 GG had a higher frequency in HBeAg positive patients (P = 0.032) and STAT4 rs7574865 GG genotype appeared more frequently in Genotype C virus infected patients (P = 0.005). In addition, Uygurs have higher frequencies of HLA‐DP/DQ protective alleles (72.5% for rs3077, 76.6% for rs9277535 and 26.8% for rs7453920) than Tibetans (51.7% for rs3077, 52.5% for rs9277535 and 18.5% for rs7453920)(all P < 0.05), and a lower prevalence of HBV infection as previously reported.

Conclusions

HLA‐DP/DQ but not IL‐28B polymorphisms correlate with HBV natural clearance, irrespective of race, and HLA‐DP/DQ would be causative genes attributing to varying prevalence in different regions. STAT4 rs7574865 seemed to be population specific in Tibetans and it might synergistically interact with virus contributing to disease progression.
Nesting ecology of East Pacific green turtles at Playa Cabuyal, Gulf of Papagayo, Costa Rica
Authors: Santidrián Tomillo Pilar , Roberts Spencer A. , Hernández Ricardo , Spotila James R. , Paladino Frank V.
Published: July 2014

East Pacific green turtles (Chelonia mydas), often referred to as black turtles, are smaller and exhibit a lower reproductive output than other populations of green turtles in the Atlantic, Indian and Western Pacific Oceans. Knowledge of nesting ecology of East Pacific green turtles is limited to general descriptions. We conducted an exhaustive analysis of the nesting ecology of East Pacific green turtles at Playa Cabuyal, North Pacific Costa Rica. Compared with other populations of green turtles, East Pacific turtles exhibited smaller clutch sizes (mean ± SD: 76.9 ± 18.2 eggs per clutch), but the number of clutches (estimated clutch frequency (ECF): 4.3 ± 2.3 clutches) fell within the upper limit reported for green turtles. Clutch size and seasonal reproductive output (409 ± 135 eggs per female), but not ECF, increased with female size. The observed internesting period (OIP) between consecutive oviposition events (mean ± SD: 15.4 ± 2.9 days) increased as the season progressed and was approximately 2 days longer than the mean OIP reported for the species. Most clutches were laid in the upper vegetated part of beach (zone 3, 75%) and within this zone, tended to be located underneath trees (79%). Hatching success of clutches laid underneath trees was significantly higher (0.89 ± 0.17) than that of clutches laid in the exposed areas of zone 3 (0.75 ± 0.33). Mean duration of the nesting process (3:14 h) was on average 45 min longer than previously reported for the species. Frequency of false crawls was high (49% of nesting activities), and nesting success was low (54% of nesting attempts). Poaching of eggs, tourism and predation by dogs were important threats to this population. Conservation actions were being successfully implemented at the local level due to presence of beach patrollers, but official protection is needed for the preservation of the nesting population into the future.
Habitat provision of barnacle tests for overcrowded periwinkles
Authors: Silva Ana C. F. , Mendonça Vanessa , Paquete Rita , Barreiras Nuno , Vinagre Catarina
Published: July 2014

In habitats where competition for space is a shaping force of animal distribution such as in the intertidal rocky ecosystem, new habitats are readily taken by colonising species. We examined the importance of empty Chthamalus spp. tests as a habitat for the intertidal common periwinkle Melaraphe neritoides on Portuguese rocky shores. The role played by the space between neighbouring barnacles as a habitat for other species has been largely studied with regard to how an ecosystem functions, whereas the equivalent role of empty barnacle tests remains largely unknown. The small periwinkle is one of the most abundant snails in European rocky shores and is an important prey for key mobile predators. Biological facilitation is common in the rocky intertidal zone, where biological structures often potentiate the abundance of other species. The role played by barnacles as biological facilitators through habitat provision is not fully understood. In this study, the abundance and morphometric features of empty barnacle tests and their occupants were examined across shore levels and shores with differing exposures, as these are important gradients explaining barnacle distribution. The availability of empty barnacle tests was also experimentally manipulated to examine the percentage, time and length of occupation. Empty barnacles were more abundant on the midshore of sheltered shores and barnacle tests were wider on the upper shore but taller on the midshore. The minimum barnacle test occupation rate by the periwinkle was 70%. Barnacle shell height was an important factor determining snail occupation, where taller barnacles harboured significantly more, but not necessarily larger, snails. Snails outside the barnacle tests were significantly larger than those found within, suggesting that this crustacean group has an increased importance as a habitat for juvenile snails, thus potentially influencing the population dynamics of M. neritoides. We found that occupation of experimentally created empty barnacles was extremely high (70%) on the day after, and remained at 100% after 3 months of monitoring. Our study is the first of its kind to focus on the features of barnacle tests that snails occupy and their occupying snail traits. According to our results, it is clear that barnacles have an important role in providing additional habitat for young gastropods. The small periwinkle is an important grazer and prey for intertidal and subtidal foraging predators; hence, the potential refuge role of barnacle tests for juvenile M. neritoides may be important in the dynamics of intertidal communities.
Chromosomal variation segregates within incipient species and correlates with reproductive isolation
Authors: Charron Guillaume , Leducq Jean‐Baptiste , Landry Christian R.
Published: July 2014

Reproductive isolation is a critical step in the process of speciation. Among the most important factors driving reproductive isolation are genetic incompatibilities. Whether these incompatibilities are already present before extrinsic factors prevent gene flow between incipient species remains largely unresolved in natural systems. This question is particularly challenging because it requires that we catch speciating populations in the act before they reach the full‐fledged species status. We measured the extent of intrinsic postzygotic isolation within and between phenotypically and genetically divergent lineages of the wild yeast Saccharomyces paradoxus that have partially overlapping geographical distributions. We find that hybrid viability between lineages progressively decreases with genetic divergence. A large proportion of postzygotic inviability within lineages is associated with chromosomal rearrangements, suggesting that chromosomal differences substantially contribute to the early steps of reproductive isolation within lineages before reaching fixation. Our observations show that polymorphic intrinsic factors may segregate within incipient species before they contribute to their full reproductive isolation and highlight the role of chromosomal rearrangements in speciation. We propose different hypotheses based on adaptation, biogeographical events and life history evolution that could explain these observations.
Validation of male sex‐specific UBC‐8071200ISSR marker and its conversion into sequence tagged sites marker in Jojoba: a high precision oil yielding dioecious shrub
Authors: Heikrujam Monika , Sharma Kuldeep , Kumar Jatin , Agrawal Veena
Published: July 2014

There is a recent surge in the marker‐assisted selection of desired sex type among economically important dioecious crops. Simmondsia chinensis (Jojoba), a dioecious crop is of immense agricultural importance where only the female plants are preferred for commerce. DNA fingerprinting technology, ISSR analysis along with bulk segregant analysis (BSA), has been carried out on a diverse set of 17‐ to18‐year‐old mature male and female plants of Jojoba to validate a male sex‐specific ISSR marker, UBC‐8071200 on larger population that comprises 330 female and 255 male plants of Jojoba. This male sex‐specific DNA fragment of ~1200 bp was cloned and sequenced. The sequence was found to be 1120 bp in length and based on the sequence information, a pair of sequence tagged sites primers was developed that amplified a single ~800 bp band, consistently only in all the male populations while no amplification was seen in their female counterparts. The marker was named as Jojoba Male Sex Marker which was further validated on 330 female plants from 22 genotypes and 255 male plants from 17 genotypes.
Graft‐transmissible movement of inverted‐repeat‐induced siRNA signals into flowers
Authors: Zhang Wenna , Kollwig Gregor , Stecyk Ewelina , Apelt Federico , Dirks Rob , Kragler Friedrich
Published: July 2014

In plants, small interfering RNAs (siRNA) and microRNAs move to distant tissues where they control numerous developmental and physiological processes such as morphogenesis and stress responses. Grafting techniques and transient expression systems have been employed to show that sequence‐specific siRNAs with a size of 21–24 nucleotides traffic to distant organs. We used inverted‐repeat constructs producing siRNA targeting the meiosis factor DISRUPTED MEIOTIC cDNA 1 (DMC1) and GFP to test whether silencing signals move into meiotically active tissues. In grafted Nicotiana tabacum, a transgenic DMC1 siRNA signal made in source tissues preferably entered the anthers formed in the first flowers. Here, the DMC1 siRNA interfered with meiotic progression and, consequently, the flowers were at least partially sterile. In agro‐infiltrated N. benthamiana plants, a GFP siRNA signal produced in leaves was allocated and active in most flower tissues including anthers. In hypocotyl‐grafted Arabidopsis thaliana plants, the DMC1 silencing signal consistently appeared in leaves, petioles, and stem, and only a small number of plants displayed DMC1 siRNA signals in flowers. In all three tested plant species the systemic silencing signal penetrated male sporogenic tissues suggesting that plants harbour an endogenous long‐distance small RNA transport pathway facilitating siRNA signalling into meiotically active cells.
Adenosine modulates light responses of rat retinal ganglion cell photoreceptors througha cAMP‐mediated pathway
Authors: Sodhi Puneet , Hartwick Andrew T. E.
Published: July 2014

Key points

Melanopsin‐containing ganglion cell photoreceptors are post‐synaptic neurons and their light responses could therefore be modified by extracellular neuromodulators present in the mammalian retina.

In this study, we show that the duration of light‐evoked spiking in these intrinsically photoreceptive retinal ganglion cells (ipRGCs) is significantly lengthened following elevation of intracellular cyclic AMP (cAMP) levels.

Furthermore, we demonstrate that adenosine, a retinal neuromodulator released at night and after dark adaptation, significantly reduced light‐evoked ipRGC spiking through suppression of the cAMP‐related pathway.

The effects of adenosine were mediated through activation of A1 receptors present on ipRGCs.

Adenosine‐mediated modulation of ipRGCs may represent an internal regulatory mechanism that influences a variety of light‐regulated processes such as circadian rhythm photoentrainment, pupil constriction and sleep/wakefulness.

Adenosine is an established neuromodulator in the mammalian retina, with A1 adenosine receptors being especially prevalent in the innermost ganglion cell layer. Activation of A1 receptors causes inhibition of adenylate cyclase, decreases in intracellular cyclic AMP (cAMP) levels and inhibition of protein kinase A (PKA). In this work, our aim was to characterize the effects of adenosine on the light responses of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to determine whether these photoreceptors are subject to neuromodulation through intracellular cAMP‐related signalling pathways. Using multielectrode array recordings from postnatal and adult rat retinas, we demonstrated that adenosine significantly shortened the duration of ipRGC photoresponses and reduced the number of light‐evoked spikes fired by these neurons. The effects were A1 adenosine receptor‐mediated, and the expression of this receptor on melanopsin‐containing ipRGCs was confirmed by calcium imaging experiments on isolated cells in purified cultures. While inhibition of the cAMP/PKA pathway by adenosine shortened ipRGC light responses, stimulation of this pathway with compounds such as forskolin had the opposite effect and lengthened the duration of ipRGC spiking. Our findings reveal that the modification of ipRGC photoresponses through a cAMP/PKA pathway is a general feature of rat ganglion cell photoreceptors, and this pathway can be inhibited through activation of A1 receptors by adenosine. As adenosine levels in the retina rise at night, adenosinergic modulation of ipRGCs may serve as an internal regulatory mechanism to limit transmission of nocturnal photic signals by ipRGCs to the brain. Targeting retinal A1 adenosine receptors for ipRGC inhibition represents a potential therapeutic target for sleep disorders and migraine‐associated photophobia.
A theoretical comparison of tissue parameter extraction methods for dual energy computed tomography
Authors: Tremblay Jean‐Étienne , Bedwani Stéphane , Bouchard Hugo
Published: July 2014

Purpose:

To evaluate the reliability of common sinogram‐based DECT reconstruction methods for radiotherapy tissue characterization and to evaluate the advantage of combining them with a stoichiometric calibration.

Methods:

The sinogram‐based DECT method defined by Alvarez and Macovski [“Energy‐selective reconstructions in x‐ray computerized tomography,” Phys. Med. Biol. 21, – (1976)] is adapted to the XCOM photon cross sections database and also generalized to a two‐material decomposition method. A theoretical framework is developed using a test phantom containing human tissue compositions for comparing the sinogram‐based methods and the calibration‐based method, being defined as the application of the stoichiometric calibration technique of Bourque et al. [“A stoichiometric calibration method for dual energy computed tomography,” Phys. Med. Biol. 59, 2059–2088 (2014)] on monoenergetic images being generated with a sinogram‐based method. Applying a bias correction to the sinogram‐based method, its performance in extracting human tissue parameters in the presence of noise as well as by altering the photon energy spectrum is compared to the calibration‐based method.

Results:

In the absence of noise and without spectrum alteration, the calibration‐based method is found to have no benefit on the sinogram‐based method. However, the calibration‐based method is shown to be potentially more reliable than bias‐corrected sinogram‐based methods in situations comparable to the clinical environment, where noise is present and the photon energy spectra can differ from what is used during image reconstruction. In determining electron density, the performance of all methods is comparable in the presence of noise only. Moreover, combined with heavy spectrum alteration, the mean errors on electron density are found higher in sinogram‐based methods in comparison with the calibration‐based method, with 1.2% versus 0.2%. In the presence of significant noise, bias‐corrected sinogram‐based methods yield mean errors on effective atomic number of about 2.5%, as compared to 0.5% for the calibration‐based method. When combined with heavy spectrum alteration, bias‐corrected sinogram‐based methods can lead to error of up to 4% on the effective atomic number versus 1.8% for the calibration‐based method.

Conclusions:

While sinogram‐based methods have the advantage of eliminating beam hardening effects, results of this study suggest improvements in the accuracy and reliability of extracting tissue parameters by applying the DECT stoichiometric calibration of Bourqueet al. to monoenergetic images being generated with such DECT reconstruction methods.
Distinct Effects of Sorbic Acid and Acetic Acid on the Electrophysiology and Metabolism of Bacillus subtilis
Authors: van Beilen J. W. A. , Teixeira de Mattos M. J. , Hellingwerf K. J. , Brul S.
Published: July 2014

Sorbic acid and acetic acid are among the weak organic acid preservatives most commonly used to improve the microbiological stability of foods. They have similar pK
a
values, but sorbic acid is a far more potent preservative. Weak organic acids are most effective at low pH. Under these circumstances, they are assumed to diffuse across the membrane as neutral undissociated acids. We show here that the level of initial intracellular acidification depends on the concentration of undissociated acid and less on the nature of the acid. Recovery of the internal pH depends on the presence of an energy source, but acidification of the cytosol causes a decrease in glucose flux. Furthermore, sorbic acid is a more potent uncoupler of the membrane potential than acetic acid. Together these effects may also slow the rate of ATP synthesis significantly and may thus (partially) explain sorbic acid's effectiveness.
Haloalkylphosphorus Hydrolases Purified from Sphingomonas sp. Strain TDK1 and Sphingobium sp. Strain TCM1
Authors: Abe Katsumasa , Yoshida Satoshi , Suzuki Yuto , Mori Junichi , Doi Yuka , Takahashi Shouji , Kera Yoshio
Published: July 2014

Phosphotriesterases catalyze the first step of organophosphorus triester degradation. The bacterial phosphotriesterases purified and characterized to date hydrolyze mainly aryl dialkyl phosphates, such as parathion, paraoxon, and chlorpyrifos. In this study, we purified and cloned two novel phosphotriesterases from
Sphingomonas
sp. strain TDK1 and
Sphingobium
sp. strain TCM1 that hydrolyze tri(haloalkyl)phosphates, and we named these enzymes haloalkylphosphorus hydrolases (TDK-HAD and TCM-HAD, respectively). Both HADs are monomeric proteins with molecular masses of 59.6 (TDK-HAD) and 58.4 kDa (TCM-HAD). The enzyme activities were affected by the addition of divalent cations, and inductively coupled plasma mass spectrometry analysis suggested that zinc is a native cofactor for HADs. These enzymes hydrolyzed not only chlorinated organophosphates but also a brominated organophosphate [tris(2,3-dibromopropyl) phosphate], as well as triaryl phosphates (tricresyl and triphenyl phosphates). Paraoxon-methyl and paraoxon were efficiently degraded by TCM-HAD, whereas TDK-HAD showed weak activity toward these substrates. Dichlorvos was degraded only by TCM-HAD. The enzymes displayed weak or no activity against trialkyl phosphates and organophosphorothioates. The TCM-HAD and TDK-HAD genes were cloned and found to encode proteins of 583 and 574 amino acid residues, respectively. The primary structures of TCM-HAD and TDK-HAD were very similar, and the enzymes also shared sequence similarity with fenitrothion hydrolase (FedA) of
Burkholderia
sp. strain NF100 and organophosphorus hydrolase (OphB) of
Burkholderia
sp. strain JBA3. However, the substrate specificities and quaternary structures of the HADs were largely different from those of FedA and OphB. These results show that HADs from sphingomonads are novel members of the bacterial phosphotriesterase family.
Regulation of Natural mRNAs by the Nonsense-Mediated mRNA Decay Pathway
Authors: Peccarelli Megan , Kebaara Bessie W.
Published: July 2014

The nonsense-mediated mRNA decay (NMD) pathway is a specialized mRNA degradation pathway that degrades select mRNAs. This pathway is conserved in all eukaryotes examined so far, and it triggers the degradation of mRNAs that prematurely terminate translation. Originally identified as a pathway that degrades mRNAs with premature termination codons as a result of errors during transcription, splicing, or damage to the mRNA, NMD is now also recognized as a pathway that degrades some natural mRNAs. The degradation of natural mRNAs by NMD has been identified in multiple eukaryotes, including
Saccharomyces cerevisiae
,
Drosophila melanogaster
,
Arabidopsis thaliana
, and humans.
S. cerevisiae
is used extensively as a model to study natural mRNA regulation by NMD. Inactivation of the NMD pathway in
S. cerevisiae
affects approximately 10% of the transcriptome. Similar percentages of natural mRNAs in the
D. melanogaster
and human transcriptomes are also sensitive to the pathway, indicating that NMD is important for the regulation of gene expression in multiple organisms. NMD can either directly or indirectly regulate the decay rate of natural mRNAs. Direct NMD targets possess NMD-inducing features. This minireview focuses on the regulation of natural mRNAs by the NMD pathway, as well as the features demonstrated to target these mRNAs for decay by the pathway in
S. cerevisiae
. We also compare NMD-targeting features identified in
S. cerevisiae
with known NMD-targeting features in other eukaryotic organisms.
Cross Kingdom Functional Conservation of the Core Universally Conserved Threonylcarbamoyladenosine tRNA Synthesis Enzymes
Authors: Thiaville Patrick C. , El Yacoubi Basma , Perrochia Ludovic , Hecker Arnaud , Prigent Magali , Thiaville Jennifer J. , Forterre Patrick , Namy Olivier , Basta Tamara , de Crécy-Lagard Valérie
Published: July 2014

Threonylcarbamoyladenosine (t
6
A) is a universal modification located in the anticodon stem-loop of tRNAs. In yeast, both cytoplasmic and mitochondrial tRNAs are modified. The cytoplasmic t
6
A synthesis pathway was elucidated and requires Sua5p, Kae1p, and four other KEOPS complex proteins. Recent
in vitro
work suggested that the mitochondrial t
6
A machinery of
Saccharomyces cerevisiae
is composed of only two proteins, Sua5p and Qri7p, a member of the Kae1p/TsaD family (L. C. K. Wan et al., Nucleic Acids Res. 41:6332–6346, 2013,
http://dx.doi.org/10.1093/nar/gkt322
). Sua5p catalyzes the first step leading to the threonyl-carbamoyl-AMP intermediate (TC-AMP), while Qri7 transfers the threonyl-carbamoyl moiety from TC-AMP to tRNA to form t
6
A. Qri7p localizes to the mitochondria, but Sua5p was reported to be cytoplasmic. We show that Sua5p is targeted to both the cytoplasm and the mitochondria through the use of alternative start sites. The import of Sua5p into the mitochondria is required for this organelle to be functional, since the TC-AMP intermediate produced by Sua5p in the cytoplasm is not transported into the mitochondria in sufficient amounts. This minimal t
6
A pathway was characterized
in vitro
and, for the first time,
in vivo
by heterologous complementation studies in
Escherichia coli
. The data revealed a potential for TC-AMP channeling in the t
6
A pathway, as the coexpression of Qri7p and Sua5p is required to complement the essentiality of the
E. coli
tsaD
mutant. Our results firmly established that Qri7p and Sua5p constitute the mitochondrial pathway for the biosynthesis of t
6
A and bring additional advancement in our understanding of the reaction mechanism.
Towards creating the perfect electronic prescription
Authors: Dhavle Ajit A , Rupp Michael T
Published: July 2014

Significant strides have been made in electronic (e)-prescribing standards and software applications that have further fueled the adoption and use of e-prescribing. However, for e-prescribing to realize its full potential for improving the safety, effectiveness, and efficiency of prescription drug delivery, important work remains to be carried out. This perspective describes the ultimate goal of all e-prescribing stakeholders including prescribers and dispensing pharmacists: a clear, complete, and unambiguous e-prescription order that can be seamlessly received, processed, and fulfilled at the dispensing pharmacy without the need for additional clarification from the prescriber. We discuss the challenges to creating the perfect e-prescription by focusing on selected data segments and data fields that are available in the new e-prescription transaction as defined in the NCPDP SCRIPT Standard and suggest steps that could be taken to move the industry closer to achieving this vision.
Delayed diagnosis of Addison's disease: an approach to management
Authors: Mascarenhas Janice V , Jude Edward B
Published: July 2014

Addison's disease accounts for the majority of cases of adrenal failure that are detected during hospital admissions. Unfortunately, prompt diagnosis of this condition is often delayed due to varied atypical manifestations and inadequate assessment at the time of presentation. We report a case of a 52-year-old woman who was detected to have hypotension during routine colonoscopy for evaluation of anaemia and progressive weight loss. During admission for evaluation of hypotension, she was also detected to have hyponatremia. Hyponatremia and hypotension failed to improve despite fluid resuscitation. Our endocrinological opinion was sought for and on further evaluation she was diagnosed with primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy were eventually instituted, which was followed by restoration of blood pressure and normalisation of serum sodium levels.
Clinical findings just after return to play predict hamstring re-injury, but baseline MRI findings do not
Authors: De Vos Robert-Jan , Reurink Gustaaf , Goudswaard Gert-Jan , Moen Maarten H , Weir Adam , Tol Johannes L
Published: July 2014

Background

Acute hamstring re-injuries are common and hard to predict. The aim of this study was to investigate the association between clinical and imaging findings and the occurrence of hamstring re-injuries.

Methods

We obtained baseline data (clinical and MRI findings) of athletes who sustained an acute hamstring injury within 5 days of initial injury. We also collected data of standardised clinical tests within 7 days after return to play (RTP). The number of re-injuries was recorded within 12 months. We analysed the association between the possible predictive variables and re-injuries with a multivariate Cox proportional-hazards regression model.

Results

Eighty patients were included at baseline and 64 patients could be included in the final analysis because data after RTP were not available in 16 cases. There were 17 re-injuries (27%). None of the baseline MRI findings were univariately associated with re-injury. A higher number of previous hamstring injuries (adjusted OR (AOR) 1.33; 95% CI 1.11 to 1.61), more degrees of active knee extension deficit after RTP (AOR 1.13; 95% CI 1.03 to 1.25), isometric knee flexion force deficit at 15° after RTP (AOR 1.04; 95% CI 1.01 to 1.07) and presence of localised discomfort on hamstring palpation after RTP (AOR 3.95; 95% CI 1.38 to 11.37) were significant independent predictors of re-injury. Athletes with localised discomfort on hamstring palpation just after RTP were consequently almost four times more likely to sustain a re-injury.

Conclusions

The number of previous hamstring injuries, active knee extension deficit, isometric knee flexion force deficit at 15° and presence of localised discomfort on palpation just after RTP are associated with a higher hamstring re-injury rate. None of the baseline MRI parameters was a predictor of hamstring re-injury.

Trial registration number

ClinicalTrial.gov numberNCT01812564.
Assessing the effect of an interactive decision-aid smartphone smoking cessation application (app) on quit rates: a double-blind automated randomised control trial protocol
Authors: BinDhim Nasser F , McGeechan Kevin , Trevena Lyndal
Published: July 2014

Introduction

In a previous study exploring the feasibility of a smoking cessation application (app), we found that about 77% of the respondents from three countries were ready to quit in the next 30 days without significant differences between countries in terms of age, operating system and number of quitting attempts. However, the efficacy of smartphone apps for smoking cessation has not yet been established. This study tests the efficacy of a smartphone smoking cessation decision-aid app compared with an app that contains only smoking cessation information.

Methods and analysis

This is an automated double-blind, randomised controlled trial of a smoking cessation app that contains the eligibility requirements and baseline questionnaire and will randomise the participants into one of the two subapps (the intervention and the control). Participants will be recruited directly from the Apple app stores in Australia, Singapore, the UK and the USA. Daily smokers aged 18 and above will be randomised into one of the subapps after completing the baseline questionnaire. Abstinence rates will be measured at 10 days, 1 month, 3 months and 6 months, with the 1-month follow-up abstinence rate as the primary outcome. Logistic regression mixed models will be used to analyse the primary outcome.

Ethics and dissemination

This study was approved by the University of Sydney's Human Ethics Committee. The results of the trial will be published in peer-reviewed journals according to the CONSORT statement.

Trial registration number

Australian New Zealand ClinicalTrial RegistryACTRN12613000833763.
Public acceptability of financial incentives for smoking cessation in pregnancy and breast feeding: a survey of the British public
Authors: Hoddinott Pat , Morgan Heather , MacLennan Graeme , Sewel Kate , Thomson Gill , Bauld Linda , Yi Deokhee , Ludbrook Anne , Campbell Marion K
Published: July 2014

Objective

To survey public attitudes about incentives for smoking cessation in pregnancy and for breast feeding to inform trial design.

Design

Cross-sectional survey.

Setting and participants

British general public.

Methods

Seven promising incentive strategies had been identified from evidence syntheses and qualitative interview data from service users and providers. These were shopping vouchers for: (1) validated smoking cessation in pregnancy and (2) after birth; (3) for a smoke-free home; (4) for proven breast feeding; (5) a free breast pump; (6) payments to health services for reaching smoking cessation in pregnancy targets and (7) breastfeeding targets. Ipsos MORI used area quota sampling and home-administered computer-assisted questionnaires, with randomised question order to assess agreement with different incentives (measured on a five-point scale). Demographic data and target behaviour experience were recorded. Analysis used multivariable ordered logit models.

Results

Agreement with incentives was mixed (ranging from 34% to 46%) among a representative sample of 1144 British adults. Mean agreement score was highest for a free breast pump, and lowest for incentives for smoking abstinence after birth. More women disagreed with shopping vouchers than men. Those with lower levels of education disagreed more with smoking cessation incentives and a breast pump. Those aged 44 or under agreed more with all incentive strategies compared with those aged 65 and over, particularly provider targets for smoking cessation. Non-white ethnic groups agreed particularly with breastfeeding incentives. Current smokers with previous stop attempts and respondents who had breast fed children agreed with providing vouchers for the respective behaviours. Up to £40/month vouchers for behaviour change were acceptable (>85%).

Conclusions

Women and the less educated were more likely to disagree, but men and women of childbearing age to agree, with incentives designed for their benefit. Trials evaluating reach, impact on health inequalities and ethnic groups are required prior to implementing incentive interventions.

Trial registration number

CRD42012001980.
Increased aortic stiffness elevates pulse and mean pressure and compromises endothelial function in Wistar rats
Authors: Guo Xiaomei , Lu Xiao , Yang Junrong , Kassab Ghassan S.
Published: July 2014

An increase in pulse pressure (PP) is highly associated with hypertension. The goal of this study was to determine the effect of increased aortic stiffness on PP and endothelial dysfunction as precursors to hypertension. A rat model of suddenly increased aortic stiffness by use of a nonconstrictive restraint (glue coating) on aortic surface was created to investigate the change of PP and mean arterial pressure (MAP). Group I ( n = 16) underwent aorta restraint for 4 wk. Group II ( n = 12) underwent aortic restraint for 4 wk, followed by restraint removal to evaluate extent of reversibility for additional 4 wk. The aortic and peripheral endothelial function was assessed by ACh-stimulated endothelium-dependent vasodilation. The level of nitrate/nitrite (NOx), endothelin-1 (ET-1), and prostacyclin (PGI2) were measured in the serum and artery tissue. We found that aortic stiffening causes a significant increase in PP and MAP ( P < 0.05). The endothelial function was markedly blunted ( P < 0.05) in both aorta and small peripheral artery. After removal of the restraint, the impaired endothelium function persisted in the aorta likely due to sustained deterioration of aortic wall, but was partially restored in peripheral artery. The endothelial dysfunction was correlated with a decrease in NOx and PGI2 ( P < 0.05) and an increase in ET-1 ( P < 0.05). Our results show that aortic stiffening results in widening of PP, which affected endothelium function through changes in synthesis of NOx, ET-1, and PGI2. These findings suggest that increased aortic stiffness may be a cause of increased PP and a precursor to hypertension.
An afferent explanation for sexual dimorphism in the aortic baroreflex of rat
Authors: Santa Cruz Chavez Grace C. , Li Bai-Yan , Glazebrook Patricia A. , Kunze Diana L. , Schild John H.
Published: July 2014

Sex differences in baroreflex (BRx) function are well documented. Hormones likely contribute to this dimorphism, but many functional aspects remain unresolved. Our lab has been investigating a subset of vagal sensory neurons that constitute nearly 50% of the total population of myelinated aortic baroreceptors (BR) in female rats but less than 2% in male rats. Termed “Ah,” this unique phenotype has many of the nonoverlapping electrophysiological properties and chemical sensitivities of both myelinated A-type and unmyelinated C-type BR afferents. In this study, we utilize three distinct experimental protocols to determine if Ah-type barosensory afferents underlie, at least in part, the sex-related differences in BRx function. Electron microscopy of the aortic depressor nerve (ADN) revealed that female rats have less myelin ( P < 0.03) and a smaller fiber cross-sectional area ( P < 0.05) per BR fiber than male rats. Electrical stimulation of the ADN evoked compound action potentials and nerve conduction profiles that were markedly different ( P < 0.01, n = 7 females and n = 9 males). Selective activation of ADN myelinated fibers evoked a BRx-mediated depressor response that was 3–7 times greater in female ( n = 16) than in male ( n = 17) rats. Interestingly, the most striking hemodynamic difference was functionally dependent upon the rate of myelinated barosensory fiber activation. Only 5–10 Hz of stimulation evoked a rapid, 20- to 30-mmHg reduction in arterial pressure of female rats, whereas rates of 50 Hz or higher were required to elicit a comparable depressor response from male rats. Collectively, our experimental results are suggestive of an alternative myelinated baroreceptor afferent pathway in females that may account for, at least in part, the noted sex-related differences in autonomic control of cardiovascular function.
Promotion of lung tumor growth by interleukin-17
Authors: Xu Beibei , Guenther James F. , Pociask Derek A. , Wang Yu , Kolls Jay K. , You Zongbing , Chandrasekar Bysani , Shan Bin , Sullivan Deborah E. , Morris Gilbert F.
Published: July 2014

Recent findings demonstrate that inhaled cigarette smoke, the predominant lung carcinogen, elicits a T helper 17 (Th17) inflammatory phenotype. Interleukin-17A (IL-17), the hallmark cytokine of Th17 inflammation, displays pro- and antitumorigenic properties in a manner that varies according to tumor type and assay system. To investigate the role of IL-17 in lung tumor growth, we used an autochthonous tumor model ( K-RasLA1mice) with lung delivery of a recombinant adenovirus that expresses IL-17A. Virus-mediated expression of IL-17A in K-RasLA1mice at 8–10 wk of age doubled lung tumor growth in 3 wk relative to littermates that received a green fluorescent protein-expressing control adenovirus. IL-17 induced matrix metalloproteinase-9 (MMP-9) expression in vivo and in vitro. In accord with this finding, selective and specific inhibitors of MMP-9 repressed the increased motility and invasiveness of IL-17-treated lung tumor cells in culture. Knockdown or mutation of p53 promoted the motility of murine lung tumor cells and abrogated the promigratory role of IL-17. Coexpression of siRNA-resistant wild-type, but not mutant, human p53 rescued both IL-17-mediated migration and MMP-9 mRNA induction in p53 knockdown lung tumor cells. IL-17 increased MMP-9 mRNA stability by reducing interaction with the mRNA destabilizing serine/arginine-rich splicing factor 1 (SRSF1). Taken together, our results indicate that IL-17 stimulates lung tumor growth and regulates MMP-9 mRNA levels in a p53- and SRSF1-dependent manner.