bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioavailability and dissolution of different formulations of oxytetracycline preparations.
Authors: Hart A , Barber HE , Calvey TN
Published: July 2012

1 The concentration of oxytetracycline in plasma was studied by microbiological assay after oral administration of five different preparations of the antibiotic. None of these preparations had been studied previously. 2 There was a statistically significant correlation between the time required for 50% dissolution at pH 2 and biological availability, as assessed by the peak plasma level or the area under the plasma concentration‐time curve. 3 The mean bioavailability of oxytetracycline was greatest with preparations of the hydrochloride, and with film‐coated tablets of the dihydrate. In contrast, sugar‐ coated tablets of oxytetracycline dihydrate were associated with poorer dissolution characteristics and reduced biological availability.
Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects
Authors: Frost Charles , Wang Jessie , Nepal Sunil , Schuster Alan , Barrett Yu Chen , Mosqueda‐Garcia Rogelio , Reeves Richard A. , LaCreta Frank
Published: July 2012

Aims

To evaluate apixaban single dose safety, tolerability, pharmacokinetics and pharmacodynamics and assess the effect of food on apixaban pharmacokinetics.

Methods

A double‐blind, placebo‐controlled, single ascending‐dose, first‐in‐human study assessed apixaban safety, pharmacokinetics and pharmacodynamics in healthy subjects randomized to oral apixaban (n = 43; 0.5–2.5 mg as solution or 5–50 mg as tablets) or placebo (n = 14) under fasted conditions. An open label, randomized, two treatment crossover study investigated apixaban pharmacokinetics/pharmacodynamics in healthy subjects (n = 21) administered apixaban 10 mg in fasted and fed states. Both studies measured apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT) or a modified PT (mPT).

Results

In the single ascending‐dose study increases in apixaban exposure appeared dose‐proportional. Median tmax occurred 1.5–3.3 h following oral administration. Mean terminal half‐life ranged between 3.6 and 6.8 h following administration of solution doses ≤2.5 mg and between 11.1 and 26.8 h for tablet doses ≥5 mg. Concentration‐related changes in pharmacodynamic assessments were observed. After a 50 mg dose, peak aPTT, INR and mPT increased by 1.2‐, 1.6‐ and 2.9‐fold, respectively, from baseline. In the food effect study: 90% confidence intervals of geometric mean ratios of apixaban Cmax and AUC in a fed vs. fasted state were within the predefined no effect (80–125%) range. Apixaban half‐life was approximately 11.5 h. The effect of apixaban on INR, PT and aPTT was comparable following fed and fasted administration.

Conclusions

Single doses of apixaban were well tolerated with a predictable pharmacokinetic/pharmacodynamic profile and a half‐life of approximately 12 h. Apixaban can be administered with or without food.
Predictors for visual dysfunction in nonfunctioning pituitary adenomas – implications for neurosurgical management
Authors: Schmalisch Kathrin , Milian Monika , Schimitzek Thilo , Lagrèze Wolf A. , Honegger Juergen
Published: July 2012

Background

Despite ample experience with surgical treatment of nonfunctioning pituitary adenomas, objective data defining the risk for visual compromise depending on the suprasellar extension in pituitary adenomas are sparse.

Design and patients

We measured the suprasellar extension of 98 newly diagnosed suprasellar nonfunctioning pituitary adenomas on sagittal and coronal magnetic resonance images using reference lines for the skull base level. In addition, the position of the optic chiasm in relation to the suprasellar adenoma was assessed. The findings were correlated with the degree of visual dysfunction and with the type of visual field defects (VFD).

Results

Seventy per cent of the patients suffered from VFD. The most frequent perimetric findings were bilateral (81·2%) or unilateral (10·1%) temporal hemifield defects. For the coronal view, a suprasellar extension of 12 mm was a practicable cut‐off value for emergence of visual disturbances (87·0% sensitivity, 72·4% specificity). For the sagittal view, 8‐mm suprasellar extension was a suitable cut‐off for appearance of chiasma syndrome (87·0% sensitivity, 75·9% specificity). In five of seven cases without a chiasma syndrome despite a suprasellar extension >12 (coronal) and 8 mm (sagittal), the optic chiasm was found in an anterior position. No correlation was found between the position of the chiasm (i.e. anterior, superior or posterior) and the type of VFD (P = 0·647). A highly significant correlation was found between the decline of visual acuity and the suprasellar adenoma extension (P < 0·0001).

Conclusion

Cut‐off values possess a high sensitivity and specificity for imminent visual disturbances and are helpful for clinical decision‐making. A delayed emergence of visual dysfunction may be observed with an anterior position of the optic chiasm.
Determining the utility of the 60 min cortisol measurement in the short synacthen test
Authors: Chitale Aditi , Musonda Patrick , McGregor Alan M. , Dhatariya Ketan K.
Published: July 2012

Objective

Despite the widespread use of the short synacthen test (SST), there remains no clear consensus on sampling times for the measurement of serum cortisol that best determines adrenal reserve. We set out to establish whether there is any value in measuring serum cortisol at 60 min following administration of synacthen.

Design

Retrospective data analysis of 500 SST results measuring 0, 30 and 60 min cortisol levels after administration of 250 μg of synacthen at 2 large urban National Health Teaching Hospitals in the UK.

Patients and measurements

Individuals thought to have primary or secondary adrenal insufficiency given 250 μg of synacthen.

Measurements

Serum cortisol levels measured at 0, 30 and 60 min, looking to see how many people who had adrenal insufficiency at the 30 min sample but in whom the 60 min sample showed adequate adrenal reserve.

Results

The results from 384 people were analysed. A total of 276 had normal responses at 30 min and also at 60 min. A sum of 33 individuals had ‘insufficient’ (i.e., <550 nmol/l) 30 min cortisol levels, rising to ≥ 550 nmol/l at the 60 min test. All 75 individuals who were insufficient at 60 min were also insufficient at 30 min. No individuals passed (≥550 nmol/l) at 30 min and then failed (<550 nmol/l) at 60 min.

Conclusions

These results suggest that a significant proportion of people undergoing a SST may be inappropriately diagnosed as having adrenal insufficiency if the 60 min sample is not measured. We suggest that the 60 min sample is measured in all individuals having a SST to prevent unnecessary over‐diagnosis of adrenal insufficiency.
Influence of lysozyme complexation with purified Aldrich humic acid on lysozyme activity
Authors: Li Y. , Tan W. F. , Wang M. X. , Liu F. , Weng L. P. , Norde W. , Koopal L. K.
Published: July 2012

Humic acid is an important component of dissolved organic matter and in two previous papers it has been shown that purified Aldrich humic acid (PAHA) forms strong complexes with the oppositely charged protein lysozyme (LSZ). The complexation and aggregation of enzymes with humic acids may lead to changes in their activity. Therefore, the enzyme activity of LSZ in the PAHA – LSZ complex as a function of mass ratio PAHA:LSZ was investigated at two pH values (pH 5 and pH 8 where PAHA and LSZ are oppositely charged) and two ionic strengths (5 mmol l−1; 50 mmol l−1). The newly prepared complex was characterized and the mass ratios PAHA:LSZ at the isoelectric point (IEP) of the complex at the assayed conditions were obtained with the Mütek particle charge detector. The LSZ activity was measured with an assay specific for LSZ. The activity of LSZ decreased upon complex formation with PAHA and the PAHA effect on the enzyme activity was increased by the subsequent aggregation. A critical PAHA:LSZ mass ratio for the behaviour of the enzyme activity was that at the IEP of the complex. Before this mass ratio was reached the LSZ activity strongly decreased under all conditions. Beyond this mass ratio both pH and ionic strength affected the activity of LSZ in the complex. The results can be explained by the effects that pH and ionic strength have on (i) the electrostatic attraction between LSZ and PAHA in the complex and (ii) the electrostatic repulsion between the complexes. These two factors plus the hydrophobic attraction determine the structure of the complexes and the size of the aggregates and hence the screening of the active site of the protein.
Elevated CO2 concentrations affect the elemental stoichiometry and species composition of an experimental phytoplankton community
Authors: VERSCHOOR ANTONIE M. , VAN DIJK MARK A. , HUISMAN JEF , VAN DONK ELLEN
Published: July 2012

1. Rising atmospheric CO2 concentrations might affect the primary production and community composition of freshwater ecosystems.

2. We investigated these potential effects in laboratory mesocosms (Limnotrons), using monoculture experiments and competition experiments with the green alga Scenedesmus obliquus and the cyanobacterium Synechocystis sp. PCC6803. The Limnotrons were sparged with ambient air (controls, 380 parts per million volume (ppmv) CO2), moderately elevated CO2 levels (3000 ppmv CO2) or highly elevated CO2 levels (18 800 ppmv CO2).

3. Growth at ambient air led to the depletion of dissolved CO2 during algal bloom development and hence a high pH. In contrast, growth at elevated CO2 levels resulted in high concentrations of dissolved CO2 and dissolved inorganic carbon (DIC), lower pH and low concentrations of nitrate and soluble reactive phosphorus. Elevated CO2 levels did not have a significant effect on the biomass of the algal species, but shifted their elemental composition towards higher carbon‐to‐nutrient ratios.

4. Competition experiments at ambient air were driven mainly by competition for inorganic carbon. In this case, the cyanobacterium Synechocystis was displaced by the green alga Scenedesmus. Elevated CO2 alleviated the community from carbon limitation, which shifted the species interactions towards competition for nitrogen and phosphorus, and resulted in coexistence of the two species. Hence, our findings do not support the hypothesis that cyanobacteria are generally better competitors for inorganic carbon than green algae.

5. In conclusion, our results show that elevated CO2 levels may cause major changes in freshwater ecosystems, including a reduction in pH, shifts in resource limitation patterns, and changes in the ecological stoichiometry and species composition of phytoplankton communities.
Male great tit song perch selection in response to noise‐dependent female feedback
Authors: Halfwerk Wouter , Bot Sander , Slabbekoorn Hans
Published: July 2012

1. Anthropogenic noise can affect intra‐pair communication and therefore interfere with reproductive success. However, many animals have various signal strategies to cope with noise, although it is unclear whether they rely on direct auditory feedback from their own perception of noise or signal‐to‐noise level or on indirect social feedback from receivers.

2. We studied the role of social feedback on male great tit (Parus major) song adjustment by exclusively exposing females to artificial traffic noise inside their nest box.

3. We found a delay in female response latencies to male song in the noisy condition compared to the control condition on the first day of noise exposure. Males from the noise treatment group, not directly exposed to noise themselves, sang closer to the nest box within 3 days after the start of exposure.

4. The male's closer proximity to the nest box most likely led to the observed higher song amplitudes at the noisy nest boxes compared to quiet control nest boxes, and explains why the inside signal‐to‐noise ratios were restored to equal levels between treatment and control nest boxes after several days of exposure.

5. The initial difference between treatment groups in female response latencies at the start of exposure also disappeared accordingly.

6. Our results strongly suggest an active role for female birds in steering male song behaviour under noisy conditions. Males did not receive direct exposure during intra‐pair communication, but adjusted their behaviour in the predicted direction. These data are important to understand the mechanisms related to communication in noise and reveal the critical role of ecology in shaping animal interactions.
Impaired retrograde membrane traffic through endosomes in a mutant CHO cell defective in phosphatidylserine synthesis
Authors: Lee Shoken , Uchida Yasunori , Emoto Kazuo , Umeda Masato , Kuge Osamu , Taguchi Tomohiko , Arai Hiroyuki
Published: July 2012

Phosphatidylserine (PS), a relatively minor constituent in the plasma membrane (PM), participates in various cellular processes such as clearance of apoptotic cells and recruitment of signaling molecules. PS also localizes in the membranes of endocytic organelles, such as recycling endosomes (REs). We recently showed that in REs, PS binds to the pleckstrin homology (PH) domain of evectin‐2, thereby regulating retrograde traffic from REs to the Golgi. However, direct evidence that PS has a role in retrograde traffic is lacking. Here, we examined the contribution of PS to endosomal membrane traffic by exploiting a mutant CHO cell line (PSA‐3) that is defective in PS synthesis. In PSA‐3 cells, the Golgi localization of TGN38, a protein that circulates between the Golgi and the PM through endosomes by retrograde traffic, was abolished, whereas the localizations of other organelle markers remained unchanged. Increasing the cellular PS level by adding ethanolamine to the culture medium restored the Golgi localization of TGN38. Tracking the endocytic fate of cell surface TGN38 that was labeled by anti‐TGN38 antibody showed that retrograde transport of TGN38 was impaired at endosomes, not at the PM. These findings provide direct evidence that intracellular PS is required for retrograde traffic through endosomes.
The role of harvest residue in rotation cycle carbon balance in loblolly pine plantations. Respiration partitioning approach
Authors: Noormets Asko , McNulty Steve G. , Domec Jean‐Christophe , Gavazzi Michael , Sun Ge , King John S.
Published: July 2012

Timber harvests remove a significant portion of ecosystem carbon. While some of the wood products moved off‐site may last past the harvest cycle of the particular forest crop, the effect of the episodic disturbances on long‐term on‐site carbon sequestration is unclear. The current study presents a 25 year carbon budget estimate for a typical commercial loblolly pine plantation in North Carolina, USA, spanning the entire rotation cycle. We use a chronosequence approach, based on 5 years of data from two adjacent loblolly pine plantations. We found that while the ecosystem is very productive (GEP up to 2900 g m−2 yr−1, NEE at maturity about 900 g C m−2 yr−1), the production of detritus does not offset the loss of soil C through heterotrophic respiration (RH) on an annual basis. The input of dead roots at harvest may offset the losses, but there remain significant uncertainties about both the size and decomposition dynamics of this pool. The pulse of detritus produced at harvest resulted in a more than 60% increase in RH. Contrary to expectations, the peak of RH in relation to soil respiration (SR) did not occur immediately after the harvest disturbance, but in years 3 and 4, suggesting that a pool of roots may have remained alive for the first few years. On the other hand, the pulse of aboveground RH from coarse woody debris lasted only 2 years. The postharvest increase in RH was offset by a decrease in autotrophic respiration such that the total ecosystem respiration changed little. The observed flux rates show that even though the soil C pool may not necessarily decrease in the long‐term, old soil C is definitely an active component in the site C cycle, contributing about 25–30% of the RH over the rotation cycle.
No stimulation of nitrogen fixation by non‐filamentous diazotrophs under elevated CO2 in the South Pacific
Authors: Law Cliff S. , Breitbarth Eike , Hoffmann Linn J. , McGraw Christina M. , Langlois Rebecca J. , LaRoche Julie , Marriner Andrew , Safi Karl A.
Published: July 2012

Nitrogen fixation by diazotrophic cyanobacteria is a critical source of new nitrogen to the oligotrophic surface ocean. Research to date indicates that some diazotroph groups may increase nitrogen fixation under elevated pCO2. To test this in natural plankton communities, four manipulation experiments were carried out during two voyages in the South Pacific (30–35oS). High CO2 treatments, produced using 750 ppmv CO2 to adjust pH to 0.2 below ambient, and ‘Greenhouse’ treatments (0.2 below ambient pH and ambient temperature +3 °C), were compared with Controls in trace metal clean deckboard incubations in triplicate. No significant change was observed in nitrogen fixation in either the High CO2 or Greenhouse treatments over 5 day incubations. qPCR measurements and optical microscopy determined that the diazotroph community was dominated by Group A unicellular cyanobacteria (UCYN‐A), which may account for the difference in response of nitrogen fixation under elevated CO2 to that reported previously for Trichodesmium. This may reflect physiological differences, in that the greater cell surface area:volume of UCYN‐A and its lack of metabolic pathways involved in carbon fixation may confer no benefit under elevated CO2. However, multiple environmental controls may also be a factor, with the low dissolved iron concentrations in oligotrophic surface waters limiting the response to elevated CO2. If nitrogen fixation by UCYN‐A is not stimulated by elevated pCO2, then future increases in CO2 and warming may alter the regional distribution and dominance of different diazotroph groups, with implications for dissolved iron availability and new nitrogen supply in oligotrophic regions.
The costs of keeping cool in a warming world: implications of high temperatures for foraging, thermoregulation and body condition of an arid‐zone bird
Authors: du Plessis Katherine L. , Martin Rowan O. , Hockey Philip A. R. , Cunningham Susan J. , Ridley Amanda R.
Published: July 2012

Recent mass mortalities of bats, birds and even humans highlight the substantial threats that rising global temperatures pose for endotherms. Although less dramatic, sublethal fitness costs of high temperatures may be considerable and result in changing population demographics. Endothermic animals exposed to high environmental temperatures can adjust their behaviour (e.g. reducing activity) or physiology (e.g. elevating rates of evaporative water loss) to maintain body temperatures within tolerable limits. The fitness consequences of these adjustments, in terms of the ability to balance water and energy budgets and therefore maintain body condition, are poorly known. We investigated the effects of daily maximum temperature on foraging and thermoregulatory behaviour as well as maintenance of body condition in a wild, habituated population of Southern Pied Babblers Turdoides bicolor. These birds inhabit a hot, arid area of southern Africa where they commonly experience environmental temperatures exceeding optimal body temperatures. Repeated measurements of individual behaviour and body mass were taken across days varying in maximum air temperature. Contrary to expectations, foraging effort was unaffected by daily maximum temperature. Foraging efficiency, however, was lower on hotter days and this was reflected in a drop in body mass on hotter days. When maximum air temperatures exceeded 35.5 °C, individuals no longer gained sufficient weight to counter typical overnight weight loss. This reduction in foraging efficiency is likely driven, in part, by a trade‐off with the need to engage in heat‐dissipation behaviours. When we controlled for temperature, individuals that actively dissipated heat while continuing to forage experienced a dramatic decrease in their foraging efficiency. This study demonstrates the value of investigations of temperature‐dependent behaviour in the context of impacts on body condition, and suggests that increasingly high temperatures will have negative implications for the fitness of these arid‐zone birds.
Insulin growth factor receptor‐1 expression and loss of PTEN protein predict early recurrence in triple‐negative breast cancer
Authors: Iqbal Jabed , Thike Aye Aye , Cheok Poh Yian , Tse Gary Man‐Kit , Tan Puay Hoon
Published: July 2012

Iqbal J, Thike A A, Cheok P Y, Tse G M‐K & Tan P H  (2012) Histopathology 61, 652–659

Insulin growth factor receptor‐1 expression and loss of PTEN protein predict early recurrence in triple‐negative breast cancer

Aims:  Insulin‐like growth factor receptor‐1 (IGFR‐1) and its signalling axis promote tumorigenesis, metastasis, and resistance to existing forms of cancer therapy, and have become a major focus for the development of anticancer drugs. As oncological management options for triple‐negative breast cancers (TNBCs) are limited, there is potential for the rapid development of novel selective anticancer agents specifically targeting components of the PTEN–phosphoinositide 3‐kinase–AKT pathway, including the phosphorylated form of AKT (pAKT) and the tumour suppressor molecule PTEN. The aim of this study was to conduct immunohistochemical analyses to examine the levels of PTEN, IGFR‐1 and pAKT expression in TNBCs, and determine whether these levels correlated with poor prognosis in this subset of aggressive breast cancers.

Methods and results:  Immunohistochemistry was performed on paraffin‐embedded tumour tissues from a consecutive cohort of 144 female patients diagnosed with TNBC. Associations of IGFR‐1, PTEN and pAKT expression with clinicopathological parameters, disease‐free survival (DFS) and overall survival (OS) were evaluated. There were significant increases in IGFR‐1 expression (99%) and pAKT expression (92%) with concomitant loss of PTEN expression in the majority of cases (63%). Increased IGFR‐1 expression and loss of PTEN expression were associated with reduced OS and DFS, respectively. pAKT expression showed a strong correlation with basal‐like expression. Combinatorial immunophenotypic analyses showed that loss of PTEN expression with concomitant IGFR‐1 expression correlated with poor DFS.

Conclusions:  A high percentage of PTEN loss with overexpression of IGFR‐1 and pAKT in TNBC indicates the potential of these molecules for predicting early recurrence and/or as targets in the formulation of effective alternative therapy regimens.
Cyclic fatigue resistance of two reciprocating nickel–titanium instruments after immersion in sodium hypochlorite
Authors: Pedullà E. , Grande N. M. , Plotino G. , Palermo F. , Gambarini G. , Rapisarda E.
Published: July 2012

Aim

To assess resistance to cyclic fatigue of reciprocating nickel–titanium (
NiTi
) files (Reciproc and WaveOne) after immersion in
NaOCl
solution over several time periods.

Methodology

A total of 90 new Reciproc R25 and WaveOne Primary were tested. The 45 files of the same brand were randomly assigned to three groups (n = 15) and submitted to the following immersion protocol in 5%
NaOCl
at 37 °C for 16 mm: no immersion (control), 1 or 5 min dynamically. The dynamic immersion and the following cyclic fatigue tests were performed using the appropriate preset reciprocation modes (‘RECIPROC ALL’ or ‘WAVEONE ALL’) in a specially designed endodontic motor. Resistance to cyclic fatigue was determined by recording time to fracture (TtF) in a stainless steel artificial canal with a 60° angle of curvature and 5 mm radius of curvature. The artificial canal was manufactured reproducing the instrument's size and taper. Data were analysed by 2‐way analyses of variance.

Results

Resistance to cyclic fatigue of the same
NiTi
file was not significantly affected by immersion in
NaOCl
. Reciproc R25 was associated with a higher cyclic fatigue resistance in all groups compared to WaveOne Primary (P < 0.0001).

Conclusions

Reciprocating dynamic immersion in
NaOCl
for 1 or 5 min did not reduce the cyclic fatigue resistance of
NiTi
files significantly. However, the type of reciprocating instrument influenced cyclic fatigue resistance with Reciproc R25 being more resistant than WaveOne Primary.
Tertiary dentinogenesis with calcium hydroxide: A review of proposed mechanisms
Authors: Sangwan P. , Sangwan A. , Duhan J. , Rohilla A.
Published: July 2012

Calcium hydroxide has been used extensively in dentistry for a century. Despite its widespread use as a pulp‐capping agent, its mechanisms of action still remain ambiguous. Understanding its modes of action will lead to a broader understanding of the mechanisms associated with induced dentinogenesis and help in optimizing the currently available agents to target specific regenerative processes to obtain the best possible clinical outcomes. A literature search relating to mechanisms of dentinogenesis of calcium hydroxide up to December 2011 was carried out using pubmed and MEDLINE database searches as well as manual searching of cross‐references from identified studies. Resulting suggestions regarding dentinogenic mechanisms of calcium hydroxide range from direct irritating action of the material to induction of release of biologically active molecules. The purpose of this article is to discuss various mechanisms through which calcium hydroxide may induce tertiary dentinogenesis in the light of observations made in included studies.
Evaluation of masticatory performance and bite force in children with sleep bruxism
Authors: KOBAYASHI F. Y. , FURLAN N. F. , BARBOSA T. S. , CASTELO P. M. , GAVIÃO M. B. D.
Published: July 2012

Summary  The aim of this study was to evaluate the association between masticatory performance (MP) and bite force (BF) in children with sleep bruxism (SB) during the mixed dentition stage, considering also the occlusal characteristics. The sample was composed by 52 healthy children of both genders, aged 6–10 years. From those, 22 presented signs and symptoms of SB and 30 were the controls. SB diagnosis consisted of both parental report and presence of tooth wear. MP was evaluated by the individual’s ability to comminute an artificial chewable test material for determining the median particle size (X50) and distribution of particles in the different sieves (b). BF was measured using a digital gnathodynamometer with fork strength of 8 mm. The results were submitted to descriptive statistics, Mann–Whitney and chi‐square tests, Spearman’s correlation and multiple logistic regression. Mean BF and X50 did not differ between groups with and without SB. A significant negative correlation was observed between BF and X50 only in the group of children with SB. Moreover, the logistic regression model showed an association between the presence of SB and higher b index. The other independent variables included in the model showed no association with SB. BF did not differ between children with and without SB. Besides, higher BFs in children with SB meant better MP; however, they were more likely to present chewed particles retained in the larger aperture sieves, consequently requiring more chewing cycles to break down the test material in smaller particles.
Genome‐wide patterns of standing genetic variation in a marine population of three‐spined sticklebacks
Authors: FEULNER PHILINE G. D. , CHAIN FRÉDÉRIC J. J. , PANCHAL MAHESH , EIZAGUIRRE CHRISTOPHE , KALBE MARTIN , LENZ TOBIAS L. , MUNDRY MARVIN , SAMONTE IRENE E. , STOLL MONIKA , MILINSKI MANFRED , REUSCH THORSTEN B. H. , BORNBERG‐BAUER ERICH
Published: July 2012

Since the end of the Pleistocene, the three‐spined stickleback (Gasterosteus aculeatus) has repeatedly colonized and adapted to various freshwater habitats probably originating from ancestral marine populations. Standing genetic variation and the underlying genomic architecture both have been speculated to contribute to recent adaptive radiations of sticklebacks. Here, we expand on the current genomic resources of this fish by providing extensive genome‐wide variation data from six individuals from a marine (North Sea) stickleback population. Using next‐generation sequencing and a combination of paired‐end and mate‐pair libraries, we detected a wide size range of genetic variation. Among the six individuals, we found more than 7% of the genome is polymorphic, consisting of 2 599 111 SNPs, 233 464 indels and structural variation (SV) (>50 bp) such as 1054 copy‐number variable regions (deletions and duplications) and 48 inversions. Many of these polymorphisms affect gene and coding sequences. Based on SNP diversity, we determined outlier regions concordant with signatures expected under adaptive evolution. As some of these outliers overlap with pronounced regions of copy‐number variation, we propose the consideration of such SV when analysing SNP data from re‐sequencing approaches. We further discuss the value of this resource on genome‐wide variation for further investigation upon the relative contribution of standing variation on the parallel evolution of sticklebacks and the importance of the genomic architecture in adaptive radiation.
Environmental stress increases selection against and dominance of deleterious mutations in inbred families of the Pacific oyster Crassostrea gigas
Authors: PLOUGH LOUIS V.
Published: July 2012

The deleterious effects of inbreeding are well documented and of major concern in conservation biology. Stressful environments have generally been shown to increase inbreeding depression; however, little is known about the underlying genetic mechanisms of the inbreeding‐by‐stress interaction and to what extent the fitness of individual deleterious mutations is altered under stress. Using microsatellite marker segregation data and quantitative trait locus (QTL) mapping methods, I performed a genome scan for deleterious mutations affecting viability (viability or vQTL) in two inbred families of the Pacific oyster Crassostrea gigas, reared in a stressful, nutrient‐poor diet and a favourable, nutrient‐rich diet, which had significant effects on growth and survival. Twice as many vQTL were detected in the stressful diet compared with the favourable diet, resulting primarily from substantially greater mortality of homozygous genotypes. At vQTL, estimates of selection (s) and dominance (h) were greater in the stressful environment ( = 0.86 vs. 0.54 and  = 0.35 vs. 0.18, in stressful and nonstressful diets, respectively). There was no evidence of interaction between vQTL. Individual vQTL differed across diets in selection only, or in both selection and dominance, and some vQTL were not affected by diet. These results suggest that stress‐associated increases in selection against individual deleterious alleles underlie greater inbreeding depression with stress. Furthermore, the finding that inbreeding‐by‐environment interaction appears, to some extent, to be locus specific, helps to explain previous observations of lineage‐specific expression of inbreeding depression and environment‐specific purging, which have important implications for conservation and evolutionary biology.
The β3‐integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks
Authors: Ristow Laura C. , Miller Halli E. , Padmore Lavinia J. , Chettri Rekha , Salzman Nita , Caimano Melissa J. , Rosa Patricia A. , Coburn Jenifer
Published: July 2012

P66 is a Borrelia burgdorferi surface protein with β3 integrin binding and channel forming activities. In this study, the role of P66 in mammalian and tick infection was examined. B. burgdorferiΔp66 strains were not infectious in wild‐type, TLR2−/−‐ or MyD88−/−‐deficient mice. Strains with p66 restored to the chromosome restored near wild‐type infectivity, while complementation with p66 on a shuttle vector did not restore infectivity. Δp66 mutants are cleared quickly from the site of inoculation, but analyses of cytokine expression and cellular infiltrates at the site of inoculation did not reveal a specific mechanism of clearance. The defect in these mutants cannot be attributed to nutrient limitation or an inability to adapt to the host environment in vivo as Δp66 bacteria were able to survive as well as wild type in dialysis membrane chambers in the rat peritoneum. Δp66 bacteria were able to survive in ticks through the larva to nymph moult, but were non‐infectious in mice when delivered by tick bite. Independent lines of evidence do not support any increased susceptibility of the Δp66 strains to factors in mammalian blood. This study is the first to define a B. burgdorferi adhesin as essential for mammalian, but not tick infection.
Coexistence of fault‐propagation and fault‐bend folding in curve‐shaped foreland fold‐and‐thrust belts: examples from the Northern Apennines (Italy)
Authors: Calamita Fernando , Pace Paolo , Satolli Sara
Published: July 2012

Terra Nova, 24, 396–406, 2012

Fault‐bend and fault‐propagation folds have unique profiles in foreland fold‐and‐thrust belts that are caused by different fault‐related folding models and controlled by the mechanical characteristic of the multilayer and/or by reactivation of normal faults in a positive inversion tectonics context. In this work, NNE–SSW‐ and NW–SE‐trending anticlines, related to the Neogene curve‐shaped Olevano‐Antrodoco‐Sibillini thrust (Northern Apennines, Italy), are investigated to reconstruct fault‐related folding mechanisms. Geological and structural analysis allows us to interpret the NNE–SSW‐trending anticlines as fault‐bend reactivation folds and the NW–SE‐trending anticlines as fault‐propagation shortcut anticlines. The coexistence of fault‐bend and fault‐propagation folding processes involving the same multi‐layered succession in different arms of a curve‐shaped thrust is explained in an inversion tectonics context. This along‐strike variation of different folding mechanisms might be recognised in similar curve‐shaped orogenic thrust‐belts controlled by structural inheritance.
The DNA‐ and RNA‐binding protein FACTOR of DNA METHYLATION 1 requires XH domain‐mediated complex formation for its function in RNA‐directed DNA methylation
Authors: Xie Meng , Ren Guodong , Zhang Chi , Yu Bin
Published: July 2012

Studies have identified a sub‐group of SGS3‐LIKE proteins including FDM1–5 and IDN2 as key components of RNA‐directed DNA methylation pathway (RdDM). Although FDM1 and IDN2 bind RNAs with 5′ overhangs, their functions in the RdDM pathway remain to be examined. Here we show that FDM1 interacts with itself and with IDN2. Gel filtration suggests that FDM1 may exist as a homodimer in a heterotetramer complex in vivo. The XH domain of FDM1 mediates the FDM1–FDM1 and FDM1–IDN2 interactions. Deletion of the XH domain disrupts FDM1 complex formation and results in loss‐of‐function of FDM1. These results demonstrate that XH domain‐mediated complex formation of FDM1 is required for its function in RdDM. In addition, FDM1 binds unmethylated but not methylated DNAs through its coiled‐coil domain. RNAs with 5′ overhangs does not compete with DNA for binding by FDM1, indicating that FDM1 may bind DNA and RNA simultaneously. These results provide insight into how FDM1 functions in RdDM.
Impacts of climate change and land‐use on the potential distribution of an invasive weed: a case study of Lantana camara in Australia
Authors: TAYLOR S , KUMAR L , REID N
Published: July 2012

Taylor S, Kumar L & Reid N (2012). Impacts of climate change and land‐use on the potential distribution of an invasive weed: a case study of Lantana camara in Australia. Weed Research.52, 391–401.

Lantana camara (lantana) is an extremely invasive species in many countries, including Australia. Biosecurity agencies will benefit from prior knowledge of the potential distribution of L. camara, under current and future climate scenarios. A process‐based niche model for this species was developed using the CLIMEX modelling package. The potential distribution generated from this model was refined by incorporating existing land‐use data in a Geographical Information System (GIS). The potential distribution of L. camara under current climate indicated that L. camara occupies almost the full extent of climatically suitable habitat available to it in Australia. Under future climate scenarios, L. camara range expands into new areas in Victoria, South Australia and Tasmania, while the northern parts of the continent become climatically unsuitable. This trend continued with the inclusion of land‐use data, although with a more restricted distri‐bution, as locations with suitable climate but unsuitable land‐use were excluded. Weed control authorities in the new areas at risk of invasion under climate change need to be alerted to this emerging threat, so that effective response measures can be taken.
Differences in timing of migration and response to sexual signalling drive asymmetric hybridization across a migratory divide
Authors: Ruegg K. , Anderson E. C. , Slabbekoorn H.
Published: July 2012

Ecological traits and sexual signals may both contribute to the process of ecological speciation. Here we investigate the roles of an ecological trait, seasonal migratory behaviour and a sexual trait, song, in restricting or directing gene flow across a migratory divide in the Swainson’s thrush (Catharus ustulatus). We show that short‐distance migratory ecotypes wintering in Central America arrive earlier at the breeding grounds than long‐distance migratory ecotypes wintering primarily in South America, providing the potential for some premating isolation. Playback experiments suggest that early‐ and late‐arriving forms recognize each other as competitors, but that the early‐arriving form responds more aggressively to a broader spectrum of stimuli. Genetic analysis suggests that hybridization occurs more often between males of the early‐arriving ecotype and females of the late‐arriving ecotype. Together our results suggest that differences in arrival times may reduce the temporal coincidence of mate choice, but asymmetry in response to heterotypic song may hinder complete divergence. These data provide further insight into the roles of ecological traits and sexual signals during the incipient stages of speciation.
Disruption of cellulose synthesis by 2,6‐dichlorobenzonitrile affects the structure of the cytoskeleton and cell wall construction in Arabidopsis
Authors: Peng L. , Zhang L. , Cheng X. , Fan L.‐S. , Hao H.‐Q.
Published: July 2012

Cellulose is the major component of plant cell walls and is an important source of industrial raw material. Although cellulose biosynthesis is one of the most important biochemical processes in plant biology, the regulatory mechanisms of cellulose synthesis are still unclear. Here, we report that 2,6‐dichlorobenzonitrile (DCB), an inhibitor of cellulose synthesis, inhibits Arabidopsis root development in a dose‐ and time‐dependent manner. When treated with DCB, the plant cell wall showed altered cellulose distribution and intensity, as shown by calcofluor white and S4B staining. Moreover, pectin deposition was reduced in the presence of DCB when immunostained with the monoclonal antibody JIM5, which was raised against pectin epitopes. This result was confirmed using Fourier transform infrared (FTIR) analysis. Confocal microscopy revealed that the organisation of the microtubule cytoskeleton was significantly disrupted in the presence of low concentrations of DCB, whereas the actin cytoskeleton only showed changes with the application of high DCB concentrations. In addition, the subcellular dynamics of Golgi bodies labelled with N‐ST‐YFP and TGN labelled with VHA‐a1‐GFP were both partially blocked by DCB. Transmission electron microscopy indicated that the cell wall structure was affected by DCB, as were the Golgi bodies. Scanning electron microscopy showed changes in the organisation of cellulose microfibrils. These results suggest that the inhibition of cellulose synthesis by DCB not only induced changes in the chemical composition of the root cell wall and cytoskeleton structure, but also changed the distribution of cellulose microfibrils, implying that cellulose plays an important role in root development in Arabidopsis.
Chorusing Behaviour in the Lusitanian Toadfish: Should I Match My Neighbours' Calling Rate?
Authors: Jordão Joana M. , Fonseca Paulo J. , Amorim Maria Clara P.
Published: July 2012

Choruses have been described mostly in birds, anurans and insects but have been poorly studied in fish. Research in batrachoidid (toadfishes) species suggest vocal facilitation among neighbouring males, but whether chorusing fish present more complex interactions is unknown. In this study, we test the hypothesis that chorusing fish males compete actively to increase attractiveness to females. We first describe vocal interactions in natural choruses of Lusitanian toadfish males. Our analysis found positive correlations between the calling rates of neighbouring males in several occasions. However, we also found that males that showed an overall low vocal activity throughout the observation period exhibited peaks of increased calling activity when neighbours decreased their calling rate, suggesting an opportunistic maximisation of attractiveness. We further test with playback experiments how toadfish males adjust calling activity relative to their neighbours'. We observed that males silent at the time of the playbacks but who had an overall high vocal performance tended to start calling when exposed to playbacks in contrast to low‐activity males. Playback experiments further showed that males initially calling at a high rate adjust their calling rate according to the neighbour's vocal activity level, that is, they increased calling rate when exposed to a high calling rate and decreased it when confronted with a low calling rate. However, males calling at a low rate did not significantly alter their calling rate when presented with a low (similar) or higher calling rate, probably due to temporary physiological and/or ecological constraints. We argue that Lusitanian toadfish males tend to optimise calling effort in relation to their neighbours when they are actively advertising. Further studies are necessary to better understand vocal behaviour with increased chorus size.
Allergic contact dermatitis to methacrylates in ECG electrode dots
Authors: Lyons Georgina , Nixon Rosemary
Published: July 2012

Acrylates are used widely in acrylic nails, dental restorative materials, paint, varnish, printing ink, adhesives, glue, orthopaedic prostheses, bone cement and diathermy pads. This is the first case of allergic contact dermatitis to methacrylates in electrocardiogram electrode dots reported in the literature.
Multiple eruptive squamous cell carcinoma in a patient with chronic plaque psoriasis on adalimumab
Authors: Simpkin Susan , Oakley Amanda
Published: July 2012

A 67‐year‐old man with chronic plaque psoriasis previously treated with psoralen plus PUVA, ciclosporin, methotrexate and acitretin developed eruptive squamous cell carcinoma after seven doses of adalimumab. We review the association of squamous cell carcinoma with immunosuppressive agents used for the treatment of chronic plaque psoriasis. Initiation of tumour necrosis factor (TNF)‐α inhibitors in a patient at high risk of non‐melanoma skin cancer may warrant chemoprophylaxis with acitretin.
Desmoplastic reaction in biopsy specimens of early colorectal cancer: A Japanese prospective multicenter study
Authors: Kimura Ryusuke , Fujimori Takahiro , Ichikawa Kazuhito , Ajioka Yoichi , Ueno Hideki , Ohkura Yasuo , Kashida Hiroshi , Togashi Kazutomo , Yao Takashi , Wada Ryo , Watanabe Toshiaki , Ochiai Atsushi , Sugai Tamotsu , Sugihara Kenichi , Igarashi Yoshinori
Published: July 2012

We previously reported that detection of desmoplastic reaction (DR) in pretreatment biopsy specimens was useful for predicting the depth of submucosal invasion (SM depth) in nonpedunculated early colorectal cancers (ECRCs) in a retrospective study. Here, we performed a prospective multicenter study for verification of our previous findings. Subjects were diagnosed with ECRC by endoscopy, and with adenocarcinoma from the biopsy specimens. Eleven institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum participated in this collaborative study. A total of 112 patients with ECRC were enrolled. For nonpedunculated ECRCs, presence of DR was significantly correlated with SM depth. The sensitivity and specificity of detection of DR for prediction of pSM2 (tumor invasion ≥1000 µm) in nonpedunculated ECRCs were 68.6% and 92.0%, respectively. Evaluation of DR in pretreatment biopsy specimens may be useful for the clinicopathological diagnosis of colorectal carcinoma with massive invasion into the submucosal layer.
Epidemiology of pleural infections in Taiwan from 1997 through 2008
Authors: SHEN HSIU‐NIEN , LU CHIN‐LI , LI CHUNG‐YI
Published: July 2012

Background and objective:  Population‐based data on pleural infections are limited. This study describes the temporal trends in the incidence, management and outcomes of pleural infections in Taiwan.

Methods:  The Taiwan National Health Insurance Research Database was used to analyse data on 26 385 patients with a first episode of pleural infection between 1997 and 2008.

Results:  During the study period, the median age of the patients increased from 60 to 65 years. The majority of patients were men (75%); this proportion remained constant over time. The standardized annual incidence of pleural infection increased from 5.2 per 100 000 in 1997 and reached a plateau of 8.4 to 9.6 per 100 000 between 2002 and 2008. Over time, there was an increase in the use of computed tomography (from 47.3% in 1997–1998 to 59.4% in 2007–2008), pigtail catheters (from 1.5% to 18.9%), fibrinolytics (from 0.9% to 9.3%) and surgery (from 27.7% to 33.6%), to treat pleural infections. Furthermore, the use of life‐support resources, including haemodialysis, mechanical ventilation and intensive care, also increased by 3.1%, 11.0% and 12.8%, respectively. Median hospital charges per patient increased by 63.6% over the 12 years. Although the proportion of patients with organ dysfunction (i.e. severe sepsis) increased from 26.5% to 47.7%, 30‐day mortality decreased from 15.0% to 13.1% (P‐value for trend = 0.001).

Conclusions:  These findings suggest that advances in the management of pleural infections and subsequent severe sepsis may have led to a reduction in the risk of short‐term mortality in Taiwan.
Update on yttrium‐90‐based radio‐embolization for treatment of hepatocellular carcinoma
Authors: Kan Raymond Wai Man , Tsang Simon Hing Yin , Poon Ronnie Tung Ping , Cheung Tan To
Published: July 2012

Background:  Catheter‐based intra‐arterial therapies provided effective tumour control for unresectable hepatocellular carcinoma without distant metastasis. There was a renewed interest in the advancement of yttrium‐90 radio‐embolization.

Method:  An extensive search on the MEDLINE databases identified seven case series and two comparative studies regarding yttrium‐90 radio‐embolization.

Results:  Case series on yttrium‐90 radio‐embolization indicated a tumour response rate that ranged from 20% to 70%, and median survival that ranged from 7.7 to 26.6 months. Two comparative studies did not demonstrate significant difference in terms of tumour response rate and survival. One of these comparative studies demonstrated a statistically significant reduction in treatment‐related neutropaenia.

Conclusion:  The current use of yttrium‐90 radio‐embolization was mainly based on small case series. Yttrium‐90 radio‐embolization seemed equivalent to conventional chemo‐embolization in terms of tumour response rate and survival benefit. Emerging evidence suggested that yttrium‐90 radio‐embolization may have a more favourable side effects profile, in particular in reducing the chance of neutropaenia. Cost and logistics arrangement were two important considerations in generalizing the application of yttrium‐90 radio‐embolization.