bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure
Authors: Núñez Julio , Núñez Eduardo , Miñana Gema , Bodí Vicent , Fonarow Gregg C. , Bertomeu‐González Vicente , Palau Patricia , Merlos Pilar , Ventura Silvia , Chorro Francisco J. , Llàcer Pau , Sanchis Juan
Published: June 2012

Aims

Recent observations in chronic stable heart failure suggest that high‐dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF).

Methods and results

We analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four‐level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all‐cause mortality. At a median follow‐up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01–1.50], but this association was not homogeneous across CA125–BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51–3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73–2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55–0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36–2.76).

Conclusion

The risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF.
Distribution and biological characteristics of Atlantic salmon (Salmo salar) at Greenland based on the analysis of historical tag recoveries
Authors: Reddin David G. , Hansen Lars Petter , Bakkestuen Vegar , Russell Ian , White Jonathan , Potter E. C. E. (Ted) , Dempson J. Brian , Sheehan Timothy F. , Ó Maoiléidigh Niall , Smith Gordon W. , Isaksson Arni , Jacobsen Jan Arge , Fowler Mark , Mork Kjell Arne , Amiro Peter
Published: June 2012

Reddin, D. G., Hansen, L. P., Bakkestuen, V., Russell, I., White, J., Potter, E. C. E., Dempson, J. B., Sheehan, T. F., Ó Maoiléidigh, N., Smith, G. W., Isaksson, A., Jacobsen, J. A., Fowler, M., Mork, K. A., and Amiro, P. 2012. Distribution and biological characteristics of Atlantic salmon (Salmo salar) at Greenland based on the analysis of historical tag recoveries. – ICES Journal of Marine Science, 69: 1589–1597. In this study, we examined 5481 records of tag recoveries at Greenland from a new tagging database held by ICES that contains information on salmon tagged in Canada, France, Faroes, Greenland, Iceland, Ireland, Norway, Spain, the UK (Northern Ireland, Scotland, England, and Wales), and the United States from the early 1960s to the present. For 4806 of the tag recoveries, latitude and longitude information were available, describing, to varying degrees of accuracy, the location of recovery of tagged fish. Release and recovery dates were variable, but no significant differences over time were noted. The information derived from tag recoveries was used to describe the distribution and growth of salmon of different origins. The proportion of recoveries from East Greenland suggested that potential multi-sea-winter salmon from northern Europe have a more easterly distribution than those from southern Europe. The location of recovery of salmon of North American origin differed from that of European salmon along the west coast of Greenland. Tag recoveries by country were not uniformly distributed across the respective NAFO Divisions. Tags from salmon originating in Canada and the United States were more commonly recovered in northern locations than tags from European-origin salmon. Analysis of rates of tag recovery suggested similar rates before and after the introduction of the NASCO Tag Return Incentive Scheme. The straight-line migration speed of both North American and European salmon changed very little over the time-series, but was ∼40% greater for North American salmon (0.43 m s−1) than for European salmon (0.29–0.32 m s−1).
Trigeminal Nerve Injury ErbB3/ErbB2 Promotes Mechanical Hypersensitivity
Authors: Ma Fei , Zhang Liping , Westlund Karin N.
Published: June 2012

Background

Chronic constriction injury of the trigeminal infraorbital nerve results in transient analgesia followed by whisker pad mechanical allodynia in rats. Neuregulin 1 expressed on axonal membranes binds receptor tyrosine kinase ErbB, promoting Schwann cell development and remyelination. This study investigated whether orofacial mechanical allodynia is signaled by ErbB3-ErbB2 heterodimers in injured nerves.

Methods

Whisker pad mechanical allodynia (von Frey stimuli) was quantified in wild type rats and in transgenic rats with Sleeping Beauty transposon mutation for neuregulin 1 transgene. Pain-related behavior was retested after intraperitoneal injection of the ErbB2 inhibitor Lapatinib, an agent shown by others to reduce breast cancer pain. Infraorbital nerve injury was evaluated histologically with myelin and neuronal biomarkers. ErbB3 changes over time were measured with western blots.

Results

Whisker pad mechanical hypersensitivity began in week 2 in wild type rats (3.11 ± 5.93 g vs. 18.72 ± 0.00 g after sham surgery, n = 9, P < 0.001), indicating trigeminal neuropathic pain, but was not evident in transgenic rats (odds ratio: 1.12, 95% confidence interval: 0.38-3.35). Initiation of statistically significant mechanohypersensitivity was delayed until week 6 after surgery in transgenic rats (3.44 ± 4.60 g vs. 18.72 ± 0.00 g, n = 4, P < 0.001). Mechanical allodynia, which persisted 8 weeks in wild type rats was alleviated by Lapatinib (15 ± 3.89 g vs. 2.45 ± 1.13 g, n = 6, P < 0.001). Infraorbital nerve damage was verified histologically. Statistically significant ErbB3 increases (weeks 5 and 10) in wild type and transgenic rats (week 10) coincided with time points when mechanical hypersensitivity was present.

Conclusion

The Neuregulin 1-ErbB3-ErbB2 complex is a causal mechanism in nerve injury-induced trigeminal neuropathic pain. Understanding peripheral glial mechanisms after nerve injury will improve neuropathic pain treatment.
Involvement of spindles in memory consolidation is slow wave sleep-specific
Authors: Cox Roy , Hofman Winni F. , Talamini Lucia M.
Published: June 2012

Both sleep spindles and slow oscillations have been implicated in sleep-dependent memory consolidation. Whereas spindles occur during both light and deep sleep, slow oscillations are restricted to deep sleep, raising the possibility of greater consolidation-related spindle involvement during deep sleep. We assessed declarative memory retention over an interval containing a nap and determined spindle density for light and deep sleep separately. In deep sleep, spindle density was considerably higher and showed a strong and robust positive correlation with retention. This relation was absent for light sleep, suggesting that the potentiating effects of spindles are tied to their co-occurrence with slow oscillations.
Cooperative D1 Degradation in the Photosystem II Repair Mediated by Chloroplastic Proteases in Arabidopsis
Authors: Kato Yusuke , Sun Xuwu , Zhang Lixin , Sakamoto Wataru
Published: June 2012

Light energy constantly damages photosynthetic apparatuses, ultimately causing impaired growth. Particularly, the sessile nature of higher plants has allowed chloroplasts to develop unique mechanisms to alleviate the irreversible inactivation of photosynthesis. Photosystem II (PSII) is known as a primary target of photodamage. Photosynthetic organisms have evolved the so-called PSII repair cycle, in which a reaction center protein, D1, is degraded rapidly in a specific manner. Two proteases that perform processive or endopeptidic degradation, FtsH and Deg, respectively, participate in this cycle. To examine the cooperative D1 degradation by these proteases, we engaged Arabidopsis (Arabidopsis thaliana) mutants lacking FtsH2 (yellow variegated2 [var2]) and Deg5/Deg8 (deg5 deg8) in detecting D1 cleaved fragments. We detected several D1 fragments only under the var2 background, using amino-terminal or carboxyl-terminal specific antibodies of D1. The appearance of these D1 fragments was inhibited by a serine protease inhibitor and by deg5 deg8 mutations. Given the localization of Deg5/Deg8 on the luminal side of thylakoid membranes, we inferred that Deg5/Deg8 cleaves D1 at its luminal loop connecting the transmembrane helices C and D and that the cleaved products of D1 are the substrate for FtsH. These D1 fragments detected in var2 were associated with the PSII monomer, dimer, and partial disassembly complex but not with PSII supercomplexes. It is particularly interesting that another processive protease, Clp, was up-regulated and appeared to be recruited from stroma to the thylakoid membrane in var2, suggesting compensation for FtsH deficiency. Together, our data demonstrate in vivo cooperative degradation of D1, in which Deg cleavage assists FtsH processive degradation under photoinhibitory conditions.
The three-dimensional coordination network in poly[di-μ3-cyanido-μ5-[5-(pyridin-4-yl)tetrazolato]-tricopper(I)]
Authors: Meng Gao-Xiang , Zhu Jian-Hui , Feng Ya-Min , Huang Xin-Tang , Yang He-Lin
Published: June 2012

In the title three-dimensional tetrazolate-based coordination polymer, poly[bis(μ3-cyanido-κ3N:C:C)[μ5-5-(pyridin-4-yl)tetrazolato-κ5N:N′:N′′:N′′′:N′′′′]tricopper(I)], [Cu3(C6H4N5)(CN)2]n, there are two types of coordinated CuIatoms. One type exhibits a tetrahedral environment and the other, residing on a twofold axis, adopts a trigonal coordination environment. The closest Cu...Cu distance is only 2.531 (2) Å, involving a bridging cyanide C atom. All four tetrazolate and the pyridine N atom of the 4-(pyridin-4-yl)-1H-tetrazolate anion are coordinated to these CuIatoms and exhibit a μ5-bridging mode. The three-dimensional coordination network can be topologically simplified as a rarely observed (3,3,4,5)-connected network with the Schläfli symbol (4.6.84)2.(42.6.87).(6.82)3.
Correlates of benzodiazepine dependence in the Netherlands Study of Depression and Anxiety
Authors: Manthey Leonie , Lohbeck Marijke , Giltay Erik J. , van Veena Tineke , Zitman Frans G. , Penninx Brenda W. J. H.
Published: June 2012

Aims

Benzodiazepines (BZDs) are effective in the short term against anxiety and insomnia. However, some BZD users develop BZD dependence after a relatively short period of time. Therefore, we aimed to identify the risk factors of BZD dependence.

Design

An observational cohort study.

Setting

The Netherlands.

Participants

Four hundred and one BZD users of the 2981 participants of the Netherlands Study of Depression and Anxiety (NESDA) were included.

Measurements

Socio‐demographic, physical, psychological, addiction‐related and BZD use‐related characteristics were investigated as possible correlates of BZD dependence severity. Dependence severity was measured by the three subscales of the Benzodiazepine Self‐Report Questionnaire, comprising problematic use, preoccupation and lack of compliance.

Findings

In multivariate analyses, problematic use was associated with more GP contacts in the past 6 months (β = 0.170, P = 0.001) and severity of insomnia (β = 0.145, P = 0.004). Preoccupation was related to anxiety severity (β = 0.194, P = 0.001), antidepressant use (β = 0.197, P < 0.001), alcohol dependence (β = 0.185, P < 0.001) and a higher daily dosage of BZD (β = 0.160, P = 0.001). Lack of compliance was associated with higher age (β = 0.122, P = 0.03), unemployment (β = 0.105, P = 0.04), insomnia (β = 0.129, P = 0.01), antidepressant use (β = 0.148, P = 0.002) and alcohol dependence (β = 0.108, P = 0.02).

Conclusions

Insomnia, antidepressant use and alcohol dependence may increase the risk of benzodiazepine dependence among individuals who use benzodiazepines.
A test of proposed new tobacco withdrawal symptoms
Authors: Etter Jean‐François , Ussher Michael , Hughes John R.
Published: June 2012

Aims 

Recent studies suggest that smoking cessation may cause more withdrawal symptoms than thought previously. The widely used Minnesota Withdrawal Scale (MWS‐R) was revised recently to include some of these newly described symptoms. We assessed the validity of MWS‐R and other proposed self‐reported measures of tobacco withdrawal symptoms.

Design and Setting 

An internet survey of daily and former smokers with repeated measurements, followed by a randomized trial among the daily smokers.

Participants 

Daily smokers (n = 1126) and former smokers (n = 3239).

Measurements 

Participants answered the original MWS (nine items), the eight additional symptoms in the MWS‐R and 23 other questions on tobacco withdrawal symptoms. Daily smokers were assigned randomly to either continue to smoke for 2 weeks or to stop smoking, and they answered follow‐up surveys 1, 3 and 7 days after their target quit date.

Findings 

Among the 31 proposed new symptoms tested by comparing recent quitters with continuing smokers, the only withdrawal‐like symptom observed was worsening of mood swings. Post‐cessation change in mood swings remained statistically significant after adjustment for baseline depression, irritability, impatience, restlessness, stress or anxiety/nervousness. Also, abstinence improved sense of smell, sense of taste and sore throat. Post‐cessation change in symptoms intensities did not predict relapse.

Conclusions 

Moods swings are a symptom of tobacco withdrawal that can be validly measured and are unpleasant. In contrast, smoking cessation also has positive, immediate effects, including improved sense of smell and taste and reduced sore throat.
Stem cell‐derived hepatocytes as a predictive model for drug‐induced liver injury: are we there yet?
Authors: Kia Richard , Sison Rowena L. C. , Heslop James , Kitteringham Neil R. , Hanley Neil , Mills John S. , Park B. Kevin , Goldring Chris E. P.
Published: June 2012

Amongst the different types of adverse drug reactions, drug‐induced liver injury is the most prominent cause of patient morbidity and mortality. However, the current available hepatic model systems developed for evaluating safety have limited utility and relevance as they do not fully recapitulate a fully functional hepatocyte, and do not sufficiently represent the genetic polymorphisms present in the population. The rapidly advancing research in stem cells raises the possibility of using human pluripotent stem cells in bridging this gap. The generation of human induced pluripotent stem cells via reprogramming of mature human somatic cells may also allow for disease modelling in vitro for the purposes of assessing drug safety and toxicology. This would also allow for better understanding of disease processes and thus facilitate in the potential identification of novel therapeutic targets. This review will focus on the current state of effort to derive hepatocytes from human pluripotent stem cells for potential use in hepatotoxicity evaluation and aims to provide an insight as to where the future of the field may lie.
Fungi are involved in the effects of litter mixtures on consumption by shredders
Authors: JABIOL JÉRÉMY , CHAUVET ERIC
Published: June 2012

1. Decomposition of litter mixtures in both terrestrial and aquatic ecosystems often shows non‐additive diversity effects on decomposition rate, generally interpreted in streams as a result of the feeding activity of macroinvertebrates. The extent to which fungal assemblages on mixed litter may influence consumption by macroinvertebrates remains unknown.

2. We assessed the effect of litter mixing on all possible three‐species combinations drawn from four tree species (Alnus glutinosa,Betula pendula,Juglans regiaandQuercus robur) on both fungal assemblages and the rate of litter consumption by a common shredder,Gammarus fossarum. After a 9‐week inoculation in a stream, batches of leaf discs were taken from all leaf species within litter mixture combinations. Ergosterol, an indicator of fungal biomass, and the composition of fungal assemblages, assessed from the conidia released, were determined, and incubated litter offered toG. fossarumin a laboratory‐feeding experiment.

3. Mixing leaf litter species enhanced both the Simpson’s index of the fungal assemblage and the consumption of litter byG. fossarum, but had no clear effect on mycelial biomass. Specifically, consumption rates ofJ. regiawere consistently higher for mixed‐species litter packs than for single‐species litter. In contrast, the consumption rates ofB. pendulawere not affected by litter mixing, because of the occurrence of both positive and negative litter‐mixing effects in different litter species combinations that counteracted each other.

4. In some litter combinations, the greater development of some fungal species (e.g.Clavariopsis aquatica) as shown by higher sporulation rates coincided with increased leaf consumption, which may have resulted from feeding preferences byG. fossarumfor these fungi.

5. Where litter mixture effects on decomposition rate are mediated via shredder feeding, this could be due to indirect effects of the fungal assemblage.
Determining vulnerability of stream communities to climate change at the landscape scale
Authors: BUSH A. , NIPPERESS D. , TURAK E. , HUGHES L.
Published: June 2012

1. As the climate changes, species are expected to shift to higher latitudes and altitudes where suitable habitat is available if dispersal is not constrained by geographic barriers. We analyse patterns of turnover in freshwater macroinvertebrate assemblages to identify which communities are most likely to be at risk from climate change, and the location of geographic barriers that could impede such adaptive range shifts.

2. We analysed macroinvertebrate data from standard biological assessments at the family level, from surveys of all coastal basins of New South Wales, Australia, covering a latitudinal gradient of more than 1000 km. We used variance partitioning to separate the variation in composition explained by climate, among‐site distance, human disturbance and other stream factors.

3. Montane stream assemblages showed high turnover in response to climatic variation. Turnover in coastal‐fringe streams was least affected by climate, but strongly correlated with distance and stream variables. Significant shifts in assemblage composition occurred between habitats within catchments and across catchment boundaries.

4. Montane stream assemblages are most vulnerable to climate change because their distribution is most responsive to climatic factors, and elevated sites are isolated from one another, reducing the scope for altitudinal migration. Dispersal limitations in coastal‐fringe assemblages will also increase their vulnerability to habitat loss from sea‐level rise. For all stream classes, the separation of many neighbouring catchment assemblages, owing to either limited dispersal or the lack of suitable habitat, is likely to constrain adaptive range shifts. This would lead to an overall reduction in beta diversity among reaches and subsequently to a reduction in landscape‐level gamma diversity.
Regulation of osteoblastic differentiation by the proteasome inhibitor bortezomib
Authors: Uyama Maki , Sato Mari M. , Kawanami Masamitsu , Tamura Masato
Published: June 2012

In eukaryotic cells, degradation of most intracellular proteins is carried out by the ubiquitin‐proteasome pathway. Recent investigations suggest that bone metabolism is also regulated by this pathway. The clinical efficacy of bortezomib, a 26S proteasome inhibitor used as an anticancer drug, has been linked to an increase in bone formation. In this study, we show that proteasome inhibitors induce expression of osteoblastic differentiation‐related genes such as osteocalcin and alkaline phosphatase in C2C12 cells. In contrast, myogenic differentiation is inhibited. Among the proteasome inhibitors tested, bortezomib induced the greatest increase in osteocalcin expression. Although these effects were similar to that of bone morphogenetic protein (BMP) 2, proteasome inhibitors did not induce transcriptional activity of Smad1/4‐dependent reporter or BMP2 signaling target gene expression. Transient transfection of osteocalcin promoter‐luciferase constructs with bortezomib resulted in an increase in luciferase activity. Mutation of OSE2, but not OSE1, sites of the osteocalcin promoter diminished the bortezomib‐induced activity. Also, Runx2 binding activity and protein levels were induced by bortezomib treatment. These results suggest that the bortezomib induces osteoblastic differentiation by modifying the activity of Runx2 and that the function of the proteasome in controlling degradation of differentiation‐related transcription factors plays an important role in osteoblast differentiation.
Dried jujube classification using support vector machine based on fractal parameters and red, green and blue intensity
Authors: Lou Heqiang , Hu Ya , Wang Bin , Lu Hongfei
Published: June 2012

A new method that combines fractal theory and red, green and blue (RGB) colour intensity was developed to sort dried jujube fruits by using support vector machine (SVM). Our result shows that the new method is fast and accurate in dried jujube fruits classification. The SVM models based on fractal parameters only achieved 85.18–92.73% total accuracy rate. The total classification accuracy of SVM based on RGB intensity values was 94.44%. However, the SVM models based on combining fractal parameters with RGB intensity values achieved 94.44–98.15% total accuracy rate. The best classification accuracy (98.15%) was found when using SVM model based on combining fractal measures (FM) with RGB intensity values (C = 512, γ = 0.0078125). Therefore, the SVM model based on combining FMs with RGB intensity is recommended in dried jujube fruits classification.
Leadership facilitation strategies to establish evidence‐based practice in an acute care hospital
Authors: Hauck Sheila , Winsett Rebecca P. , Kuric Judy
Published: June 2012

hauck s., winsett r.p. & kuric j. (2013) Leadership facilitation strategies to establish evidence‐based practice in an acute care hospital. Journal of Advanced Nursing69(3), 664–674. doi: 10.1111/j.1365‐2648.2012.06053.x

Aim.  To assess the impact of leadership facilitation strategies on nurses’ beliefs of the importance and frequency of using evidence in daily nursing practice and the perception of organizational readiness in an acute care hospital.

Background.  Integrating evidence in practice is a prominent issue for hospital nursing as knowledge and skills, beliefs, organizational infrastructure and nursing leadership must all be addressed.

Design.  Prospective, descriptive comparative.

Method.  Three surveys were used in this prospective descriptive comparative study. Evidence‐Based Practice Beliefs Scale, the Implementation Scale and Organizational Culture & Readiness for System‐Wide Integration Survey measured change before and after facilitating strategies for evidence‐based practice enculturation. Data were collected in December 2008 (N = 427) and in December 2010 (N = 469).

Results.  Leadership facilitated infrastructure development in three major areas: incorporating evidence‐based practice outcomes in the strategic plan; supporting mentors; and advocating for resources for education and outcome dissemination. With the interventions in place, the total group scores for beliefs and organizational readiness improved significantly. Analyses by job role showed that direct care nurses scores improved more than other role types. No differences were found in the implementation scores.

Conclusion.  Successful key strategies were evidence‐based practice education and establishing internal opportunities to disseminate findings. Transformational nursing leadership drives organizational change and provides vision, human and financial resources and time that empowers nurses to include evidence in practice.
Intraspecific variation in body size and the rate of reproduction in female insects – adaptive allometry or biophysical constraint?
Authors: Berger David , Olofsson Martin , Friberg Magne , Karlsson Bengt , Wiklund Christer , Gotthard Karl
Published: June 2012

1.A high rate of reproduction may be costly if ecological factors limit immediate reproductive output as a fast metabolism compromises own future survival. Individuals with more reserves need more time and opportunity to realize their reproductive potential. Theory therefore predicts that the reproductive rate, defined as the investment in early reproduction in proportion to total potential, should decrease with body size within species.

2.However, metabolic constraints on body size‐ and temperature‐dependent biological rates may impede biophysical adaptation. Furthermore, the sequential manner resources that are allocated to somatic vs. reproductive tissue during ontogeny may, when juveniles develop in unpredictable environments, further contribute to non‐adaptive variation in adult reproductive rates.

3.With a model on female egg laying in insects, we demonstrate how variation in body reserves is predicted to affect reproductive rate under different ecological scenarios. Small females always have higher reproductive rates but shorter lifespans. However, incorporation of female host selectivity leads to more similar reproductive rates among female size classes, and oviposition behaviour is predicted to co‐evolve with reproductive rate, resulting in small females being more selective in their choice and gaining relatively more from it.

4.We fed simulations with data on the butterflyPararge aegeriato compare model predictions with reproductive rates of wild butterflies. However, simulated reproductive allometry was a poor predictor of that observed. Instead, reproductive rates were better explained as a product of metabolic constraints on rates of egg maturation, and an empirically derived positive allometry between reproductive potential and size. However, fitness is insensitive to moderate deviations in reproductive rate when oviposition behaviour is allowed to co‐evolve in the simulations, suggesting that behavioural compensation may mitigate putative metabolic and developmental constraints.

5.More work is needed to understand how physiology and development together with compensatory behaviours interact in shaping reproductive allometry. Empirical studies should evaluate adaptive hypotheses against proper null hypotheses, including prediction from metabolic theory, preferentially by studying reproductive physiology in combination with behaviour. Conversely, inferences of constraint explanations on reproductive rates must take into consideration that adaptive scenarios may predict similar allometric exponents.
The evolution of a highly speciose group in a changing environment: are we witnessing speciation in the Iberá wetlands?
Authors: FERNÁNDEZ MARIA JIMENA GÓMEZ , GAGGIOTTI OSCAR E. , MIROL PATRICIA
Published: June 2012

Delimiting species is very conflicting in the case of very young taxa that are in the process of diversification, and even more difficult if the species inhabit a heterogeneous environment. In this case, even population delimitation is controversial. The South American genus of subterranean rodents Ctenomys is highly speciose, with 62 species that appeared in the lapse of 3 Myr. Within the genus, the ‘perrensi’ group, formed by three named species and a group of forms of unknown taxonomic status, inhabits the Iberá wetland, in northern Argentina. Almost every locality shows a particular chromosomal complement. To understand the relationships and the evolutionary process among species and populations, we examined mitochondrial DNA sequences and microsatellite genotypes. We found an isolation‐by‐distance pattern with evidence of cluster‐like behaviour of the system. The mitochondrial DNA network revealed two different groups, separated by one of the main rivers of the region. Clustering methods delimited 12 different populations and five metapopulation lineages that seem to be evolving independently. We found evidence of ancient migration among localities at the centre of the distribution but no signals of current migration among the 12 delimited clusters. Some of the genetic clusters found included localities with different chromosomal numbers, which points to the existence of gene flow despite chromosomal variation. The evolutionary future of these five lineages is controlled by the dynamics of their habitat: if stable, they may become distinct species; otherwise, they may collapse into a hybrid swarm, forming a single evolving metapopulation.
Spatially explicit models of dynamic histories: examination of the genetic consequences of Pleistocene glaciation and recent climate change on the American Pika
Authors: BROWN JASON L. , KNOWLES L. LACEY
Published: June 2012

A central goal of phylogeography is to identify and characterize the processes underlying divergence. One of the biggest impediments currently faced is how to capture the spatiotemporal dynamic under which a species evolved. Here, we described an approach that couples species distribution models (SDMs), demographic and genetic models in a spatiotemporally explicit manner. Analyses of American Pika (Ochotona princeps) from the sky islands of the central Rocky Mountains of North America are used to provide insights into key questions about integrative approaches in landscape genetics, population genetics and phylogeography. This includes (i) general issues surrounding the conversion of time‐specific SDMs into simple continuous, dynamic landscapes from past to current, (ii) the utility of SDMs to inform demographic models with deme‐specific carrying capacities and migration potentials as well as (iii) the contribution of the temporal dynamic of colonization history in shaping genetic patterns of contemporary populations. Our results support that the inclusion of a spatiotemporal dynamic is an important factor when studying the impact of distributional shifts on patterns of genetic data. Our results also demonstrate the utility of SDMs to generate species‐specific predictions about patterns of genetic variation that account for varying degrees of habitat specialization and life history characteristics of taxa. Nevertheless, the results highlight some key issues when converting SDMs for use in demographic models. Because the transformations have direct effects on the genetic consequence of population expansion by prescribing how habitat heterogeneity and spatiotemporal variation is related to the species‐specific demographic model, it is important to consider alternative transformations when studying the genetic consequences of distributional shifts.
Natural antisense transcripts in fungi
Authors: Donaldson Michael E. , Saville Barry J.
Published: June 2012

Fungi are models for investigating many eukaryotic molecular processes. The identification of natural antisense transcripts (NATs) in fungi led to the discovery of mechanisms for controlling gene expression through transcriptional interference, chromatin remodelling and dsRNA formation. An overview of these mechanisms and the description of specific NAT functions is provided to give context for a broader discussion of fungal NATs. Transcriptome analyses have revealed a large number of NATs in a divergent group of fungi. The timing of NAT expression suggests roles in core life functions, such as responding to the environment and sexual reproduction. The transcriptome studies also uncover a large number of NATs whose functions remain elusive. These could provide novel control of gene expression, targeted responses to stimuli, or other functions. The goal of this review is provide background for this expanding field of research while highlighting opportunities for future discoveries.
The multifaceted roles of FLOWERING LOCUS T in plant development
Authors: PIN P. A. , NILSSON O.
Published: June 2012

One of the key developmental processes in flowering plants is the differentiation of the shoot apical meristem into a floral meristem. This transition is regulated through the integration of environmental and endogenous stimuli, involving a complex, hierarchical signalling network. In arabidopsis, the FLOWERING LOCUS T (FT) protein, a mobile signal recognized as a major component of florigen, has a central position in mediating the onset of flowering. FT‐like genes seem to be involved in regulating the floral transition in all angiosperms examined to date. Evidence from molecular evolution studies suggests that the emergence of FT‐like genes coincided with the evolution of the flowering plants. Hence, the role of FT in floral promotion is conserved, but appears to be restricted to the angiosperms. Besides flowering, FT‐like proteins have also been identified as major regulatory factors in a wide range of developmental processes including fruit set, vegetative growth, stomatal control and tuberization. These multifaceted roles of FT‐like proteins have resulted from extensive gene duplication events, which occurred independently in nearly all modern angiosperm lineages, followed by sub‐ or neo‐functionalization. This review assesses the plethora of roles that FT‐like genes have acquired during evolution and their implications in plant diversity, adaptation and domestication.
International consensus on (ICON) pediatric asthma
Authors: Papadopoulos N. G. , Arakawa H. , Carlsen K.‐H. , Custovic A. , Gern J. , Lemanske R. , Le Souef P. , Mäkelä M. , Roberts G. , Wong G. , Zar H. , Akdis C. A. , Bacharier L. B. , Baraldi E. , van Bever H. P. , de Blic J. , Boner A. , Burks W. , Casale T. B. , Castro‐Rodriguez J. A. , Chen Y. Z. , El‐Gamal Y. M. , Everard M. L. , Frischer T. , Geller M. , Gereda J. , Goh D. Y. , Guilbert T. W. , Hedlin G. , Heymann P. W. , Hong S. J. , Hossny E. M. , Huang J. L. , Jackson D. J. , de Jongste J. C. , Kalayci O. , Aït‐Khaled N. , Kling S. , Kuna P. , Lau S. , Ledford D. K. , Lee S. I. , Liu A. H. , Lockey R. F. , Lødrup‐Carlsen K. , Lötvall J. , Morikawa A. , Nieto A. , Paramesh H. , Pawankar R. , Pohunek P. , Pongracic J. , Price D. , Robertson C. , Rosario N. , Rossenwasser L. J. , Sly P. D. , Stein R. , Stick S. , Szefler S. , Taussig L. M. , Valovirta E. , Vichyanond P. , Wallace D. , Weinberg E. , Wennergren G. , Wildhaber J. , Zeiger R. S.
Published: June 2012

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re‐evaluate and fine‐tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype‐specific treatment choices; however, this goal has not yet been achieved.
Frequencies of HNA‐1, HNA‐3, HNA‐4, and HNA‐5 in the Danish and Zambian populations determined using a novel TaqMan real time polymerase chain reaction method
Authors: Nielsen K. R. , Koelbaek M. D. , Varming K. , Baech J. , Steffensen R.
Published: June 2012

In this study, we report a novel real time polymerase chain reaction (Q‐PCR) method using TaqMan probes for human neutrophil antigens (HNA)‐1, ‐3, ‐4, and ‐5 genotyping. The method was validated in a Caucasian Danish population, a Zambian population, and in clinical samples using three different methods: an in‐house polymerase chain reaction with sequence‐specific primers (PCR‐SSP) method, a commercial available PCR‐SSP kit and a novel Q‐PCR method. We observed no discrepancy in the genotype frequencies determined by the PCR‐SSP methods and the TaqMan assay in the populations studied. In tests of a family of Nigerian origin and in samples carrying the rare SLC44A2*1:2 genotype, different results were produced by the commercial PCR‐SSP kit and the real‐time TaqMan assay. The TaqMan‐based genotyping method was rapid and reproducible, allowing high‐throughput HNA‐1, ‐3, ‐4, and ‐5 genotyping.
The free radical scavenger S‐PBN significantly prolongs DSG‐mediated graft survival in experimental xenotransplantation
Authors: Biglarnia Ali‐Reza , Emanuelsson Cecilia , Quach My , Clausen Fredrik , Larsson Erik , Schneider Mårten K.J. , Tufveson Gunnar , Lorant Tomas
Published: June 2012

Biglarnia A‐R, Emanuelsson C, Quach M, Clausen F, Larsson E, Schneider MKJ, Tufveson G, Lorant T. The free radical scavenger S‐PBN significantly prolongs DSG‐mediated graft survival in experimental xenotransplantation. Xenotransplantation 2012; 19: 166–176. © 2012 John Wiley & Sons A/S.

Abstract:  Background:  Nitrones such as 2‐sulfo‐phenyl‐N‐tert‐butyl nitrone (S‐PBN) are known to trap and stabilize free radicals and to reduce inflammation. Recently, S‐PBN was shown to reduce infiltration of T lymphocytes and the expression of adhesion molecules on the endothelium in experimental traumatic brain injury. We hypothesized that S‐PBN could reduce infiltration of T lymphocytes during cell‐mediated xenograft rejection and thereby increase graft survival. The concordant mouse‐to‐rat heart transplantation model was used to test the hypothesis. In this model, grafts undergo acute humoral xenograft rejection (AHXR) almost invariably on day 3 and succumb to cell‐mediated rejection on approximately day 8 if AHXR is inhibited by treatment with 15‐deoxyspergualin (DSG).

Material and methods:  Hearts from Naval Medical Research Institute (NMRI) mice were transplanted to the neck vessels of Lewis rats. Recipients were treated with S‐PBN (n = 9), DSG (n = 9), S‐PBN and DSG in combination (n = 10) or left untreated (n = 9) for survival studies. S‐PBN was given daily intraperitoneally at a dose of 150 mg/kg body weight (BW) on day −1 to 30, and DSG was given daily intraperitoneally at a dose of 10 mg/kg BW on day −1 to 4 and 5 mg/kg BW on day 5 to 21. Nine additional recipients were given S‐PBN only on days −1 and 0 in combination with continuous DSG treatment. Grafts were monitored until they stopped beating. Additional recipients were treated with S‐PBN (n = 5), DSG (n = 5), S‐PBN and DSG in combination (n = 6) or left untreated (n = 5) for morphological, immunohistochemical and flow cytometry analyses on days 2 and 6 after transplantation.

Results:  S‐PBN treatment in combination with DSG resulted in increased median graft survival compared to DSG treatment alone (14 vs. 7 days; P = 0.019). Lower number of T lymphocytes on day 6 (P = 0.019) was observed by ex vivo propagation and flow cytometry when combining S‐PBN with DSG, whereas immunohistochemical analyses demonstrated a significant reduction in the number of infiltrated CD4+, but not TCR+, cells. S‐PBN treatment alone had no impact on graft survival compared to untreated rats (3 vs. 3 days). No differences were seen in ICAM‐1 and VCAM‐1 expression or in morphology between the groups.

Conclusion:  The combination of S‐PBN and DSG treatment increases xenograft survival. The main effect of S‐PBN appears to be in direct connection with the transplantation. Because of its low toxicity, S‐PBN could become useful in combination with other immunosuppressants to reduce cell‐mediated xenograft rejection.
Islet isolation and purification from inbred Wuzhishan miniature pigs
Authors: Jiang Xiaofeng , Qian Taolai , Linn Thomas , Cao Liangqi , Xiang Guangyang , Wang Yezeng , Peng Heping , Xue Ping , Zhang Lehong , Chen De , Yang Xuewei
Published: June 2012

Jiang X, Qian T, Linn T, Cao L, Xiang G, Wang Y, Peng H, Xue P, Zhang L, Chen D, Yang X. Islet isolation and purification from inbred Wuzhishan miniature pigs. Xenotransplantation 2012; 19: 159–165. © 2012 John Wiley & Sons A/S.

Abstract:  Background:  To investigate the applicability of inbred Wuzhishan (WZS) miniature pigs for porcine islet isolation and purification.

Methods:  Islet isolation and purification was conducted on adult (1‐yr‐old), male inbred WZS miniature pigs and age‐ and sex‐matched market pigs obtained from a local slaughterhouse (control group). Pancreata were excised, and islet isolation was carried out by static digestion and discontinuous gradient centrifugation. Viability of the purified islets was tested by radioimmunochemistry assay to measure glucose‐induced insulin release in culture and transplantation in an in vivo study.

Results:  The anatomical structure of the WZS miniature pig pancreas was more similar to the human pancreas than that of the market pig. Islet yield of the WZS miniature pigs’ pancreata was significantly higher than that of the market pigs (6078 ± 1105 vs. 2500 ± 625 islet equivalents [IEQ]/g). In vitro study demonstrated that the islets isolated from WZS miniature pigs were viable, as they efficiently responded to glucose challenge. In vivo study showed that the islets from both groups could cure the diabetic rat with the survival varied from 3 to 5 days (median, 4.3 days) and 2–4 days (median, 3.6 days) in experimental group and control group, respectively.

Conclusion:  Wuzhishan miniature pig pancreas may be a feasible source of islets for xenotransplantation.
Xenotransplantation literature update, March to April 2012
Authors: Schneider Mårten K. J. , Seebach Jörg D.
Published: June 2012

Schneider MKJ, Seebach JD. Xenotransplantation literature update, March to April 2012. Xenotransplantation 2012; 19: 207–211. © 2012 John Wiley & Sons A/S.
Oral activated charcoal suppresses hyperphosphataemia in haemodialysis patients
Authors: WANG ZUNSONG , CUI MEIYU , TANG LIJUN , LI WENBIN , WEI YONG , ZHU ZHUXIAN , JIA XIAOYAN , KONG XIANGLEI , XU DONGMEI
Published: June 2012

Aim:  Hyperphosphataemia is almost inevitable in end stage renal disease (ESRD) patients and is associated with increased morbidity and mortality. In this study we examined whether oral activated charcoal (oAC) reduces serum phosphate level in haemodialysis patients.

Methods:  This was an open‐label, prospective, uncontrolled study. One hundred and thirty‐five haemodialysis patients were included in this study, with cessation of treatment with any phosphate binders during a 2 week washout period. Patients with serum phosphate levels greater than 5.5 mg/dL during the washout period were included for treatment with oAC. oAC was started at a dose of 600 mg three times per day with meals and was administered for 24 weeks. oAC dose was titrated up during the 24 week period to achieve phosphate control (3.5–5.5 mg/dL). A second 2 week washout period followed the end of oAC treatment.

Results:  In the 114 patients who successfully completed the trial, the mean dose of activated charcoal was 3190 ± 806 mg/day. oAC reduced mean phosphate levels to below 5.5 mg/dL, with mean decreases of 2.60 ± 0.11 mg/dL (P < 0.01) and 103 (90.4%) of the patients reached the phosphate target. After the second washout period the phosphate levels increased to 7.50 ± 1.03 mg/dL (P < 0.01). Serum intact parathyroid hormone (iPTH) levels declined from 338.75 ± 147.77 pg/mL to 276.51 ± 127.82 pg/mL (P < 0.05) during the study. oAC had no influence on serum prealbumin, total cholesterol, triglycerides, serum ferritin, haemoglobin or platelet levels and the levels of 1,25‐dihydroxyvitamin D were stable during the study.

Conclusion:  In this open‐label uncontrolled study, oAC effectively controls hyperphosphataemia and hyperparathyroidism in haemodialysis patients. The safety and efficacy of oAC needs to be assessed in a randomized controlled trial.
Severe refractory hypoxaemia in submassive pulmonary embolism: a surrogate marker of severe right ventricular dysfunction and indication for thrombolysis
Authors: Braude S. , Martens‐Nielsen J.
Published: June 2012

The role of thrombolysis in pulmonary thromboembolism is controversial. We describe a case of life‐threatening acute pulmonary embolism where thrombolysis was successfully administered because of extreme refractory hypoxaemia. We suggest that profound refractory hypoxaemia in this clinical setting was due to the combination of severe right ventricular dysfunction and shunting from pulmonary infarction. The shunt was not likely to have resolved in the short term, but right ventricular function and hypoxaemia improved with clot lysis. Similar clinical presentations should prompt active consideration of thrombolysis.
Clinical aspects of adult syphilis
Authors: Read P. J. , Donovan B.
Published: June 2012

Syphilis has been resurgent in Australian cities for the last decade. The varied presentation of this infection requires the physician to consider syphilis in the differential diagnosis of a broad range of conditions. Most cases are in men who have sex with men, young people in remote Aboriginal communities, or travellers from high‐prevalence countries. The diagnosis and staging of syphilis require a sexual history, physical examination and interpretation of serological and microbiological findings. Penicillin remains the mainstay of effective treatment and has been used successfully for over 65 years. Treatment failure is rare, whereas reinfection is common. The interaction of syphilis and human immunodeficiency virus is complex, but standard therapy remains curative, and lumbar puncture is rarely required. Regular testing of high‐risk individuals, contact tracing with empirical treatment and serological follow up are important components of syphilis control.
Effectiveness of adherence therapy in patients with early psychosis: A mirror image study
Authors: Brown Ellie , Gray Richard , Jones Martin , Whitfield Simon
Published: June 2012

In patients with early psychosis, medication non‐adherence is associated with more frequent relapse. Observational studies have reported that up to 60% of patients fail to take medication as prescribed. This study aimed to establish the effectiveness of adherence therapy (AT) training for two multidisciplinary early intervention in psychosis (EIIP) teams in preventing relapse in their patients. This intervention involved six 1‐day team AT training sessions delivered monthly over a 6‐month period. Participants were patients with early psychosis who were on the caseload of the EIIP teams during the study period. A mirror‐image design was used, comparing clinician ratings of relapse in the year preceding training (year 0) and the subsequent year (year 1). Results showed that in year 0, the mean number of relapses was 0.96 (standard deviation (SD) = 1.10). During year 1, relapses reduced significantly (P < 0.01) to 0.34 (SD = 0.64). No unexpected effects of training were reported. A thematic analysis of staff views of training, and service users' views of their care received from EIIP teams, was also completed. Challenges in faithfully incorporating AT skills into practice were reported. In conclusion, AT training coincided with reductions in relapse rates in patients receiving services from an EIIP team, but no other changes in outcomes were detected.