bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Controlled Trial of a Self‐Regulation Intervention for Older Adults with Asthma
Authors: Baptist Alan P. , Ross Jacqueline A. , Yang Ye , Song Peter X. K. , Clark Noreen M.
Published: April 2013

Objectives

To evaluate a self‐regulation intervention for asthma for older adults.

Design

A blinded randomized controlled trial.

Setting

Single‐center tertiary care academic center.

Participants

Seventy older adults aged 65 and older with persistent asthma randomized to an intervention or control group.

Intervention

Participants participate in a six‐session program conducted over the telephone and in group sessions. Participants selected an asthma‐specific goal, identified problems, and addressed potential barriers.

Measurements

Outcomes were assessed at 1, 6, and 12 months and included the mini‐Asthma Quality of Life Questionnaire (mAQLQ), Asthma Control Questionnaire (ACQ), healthcare utilization, exhaled nitric oxide (FENO), and percentage of predicted forced expiratory volume in 1 second (FEV1%).

Results

The mAQLQ score was significantly higher in the intervention group at 1, 6, and 12 months, even after controlling for confounding factors. The between‐group difference decreased over time, although at 12 months, it remained greater than 0.5 points. The ACQ was better in the intervention group than in the control group at 1, 6, and 12 months. At 12 months, those in the intervention group were 4.2 times as likely as those in the control group to have an ACQ score in the controlled range. Healthcare utilization was lower in the intervention group, although no difference was observed in FENO or predicted FEV1%.

Conclusion

A self‐regulation intervention can improve asthma control, quality of life, and healthcare utilization in older adults.
Neto1 associates with the NMDA receptor/amyloid precursor protein complex
Authors: Cousins Sarah L. , Innocent Neal , Stephenson F. Anne
Published: April 2013

Neuropilin tolloid‐like 1 (Neto1), is a CUB domain‐containing transmembrane protein that was recently identified as a novel component of the NMDA receptor complex. Here, we have investigated the possible association of Neto1 with the amyloid precursor protein (APP)695/GluN1/GluN2A and APP695/GluN1/GluN2B NMDA receptor trafficking complexes that we have previously identified. Neto1HA was shown to co‐immunoprecipitate with assembled NMDA receptors via GluN2A or GluN2B subunits; Neto1HA did not co‐immunoprecipitate APP695FLAG. Co‐immunoprecipitations from mammalian cells co‐transfected with APP695FLAG, Neto1HA and GluN1/GluN2A or GluN1/GluN2B revealed that all four proteins co‐exist within one macromolecular complex. Immunoprecipitations from native brain tissue similarly revealed the existence of a GluN1/GluN2A or GluN2B/APP/Neto1 complex. Neto1HA caused a reduction in the surface expression of both NMDA receptor subtypes, but had no effect on APP695FLAG‐ or PSD‐95αc‐Myc enhanced surface receptor expression. The Neto1 binding domain of GluN2A was mapped using GluN1/GluN2A chimeras and GluN2A truncation constructs. The extracellular GluN2A domain does not contribute to association with Neto1HA but deletion of the intracellular tail resulted in a loss of Neto‐1HA co‐immunoprecipitation which was paralleled by a loss of association between GluN2A and SAP102. Thus, Neto1 is concluded to be a component of APP/NMDA receptor trafficking complexes.

image

Neto1 is shown to be a constituent of APP/NMDA receptor trafficking complexes. Since Neto1 is shown to associate with GluN2 expressed alone and, APP with GluN1‐1a alone, it is proposed that trafficking complexes are formed in the endoplasmic reticulum and contribute to regulation of NMDA receptor surface expression. Alternative scenarios are depicted since it is to be determined if respective associations are direct.
Impulsivity and apathy in Parkinson's disease
Authors: Sinha Nihal , Manohar Sanjay , Husain Masud
Published: April 2013

Impulse control disorders (ICDs) and apathy are recognized as two important neuropsychiatric syndromes associated with Parkinson's disease (PD), but as yet we understand very little about the cognitive mechanisms underlying them. Here, we review emerging findings, from both human and animal studies, that suggest that impulsivity and apathy are opposite extremes of a dopamine‐dependent spectrum of motivated decision making. We first argue that there is strong support for a hypodopaminergic state in PD patients with apathy, as well as for an association between dopamine therapy and development of ICDs. However, there is little evidence for a clear dose‐response relationship, and great heterogeneity of findings. We argue that dopaminergic state on its own is an insufficient explanation, and suggest instead that there is now substantial evidence that both apathy and impulsivity are in fact multi‐dimensional syndromes, with separate, dissociable mechanisms underlying their ‘surface’ manifestations. Some of these mechanisms might be dopamine‐dependent. According to this view, individuals diagnosed as impulsive or apathetic may have very different mechanisms underlying their clinical states. We propose that impulsivity and apathy can arise from dissociable deficits in option generation, option selection, action initiation or inhibition and learning. Review of the behavioural and neurobiological evidence leads us to a new conceptual framework that might help understand the variety of functional deficits seen in PD.
In-vitro stability and metabolism of a tacrine–silibinin codrug
Authors: Zenger Katharina , Chen Xinyu , Decker Michael , Kraus Birgit
Published: April 2013

Objectives

A tacrine-silibinin codrug showed promising results in pharmacological and toxicity testing, superior to an equimolar mixture of tacrine and silibinin. The aim of this study was to get more information about its stability, possible degradation products, metabolites, and especially its active principle in vitro and in vivo.

Methods

The stability of the codrug was analysed under in-vitro assay conditions. Additionally, its metabolism was investigated using pooled human liver microsomes. Metabolites were identified via liquid chromatography-high resolution electrospray ionization mass spectrometry. Furthermore, the influence of one of the main cleavage products, tacrine hemi succinamide, on viability and mitochondria of hepatic stellate cells was analysed.

Key findings

The codrug remained stable in culture medium (Dulbecco's modified Eagle's medium) over an incubation period of 24 h, whereas exposition to microsomal enzymes led to rapid cleavage of the ester bond to form silibinin and a tacrine hemi succinamide. In addition, glucuronidated metabolites of both silibinin and the codrug were detected. For the tacrine hemi succinamide, no effects were observed with regard to cell viability and mitochondrial impairment.

Conclusions

This study helps understand and interpret previous results concerning the effects and the absence of toxicity of the tacrine–silibinin codrug and supplies important information for further identification of the active principles of the codrug in vivo.
In vitroenantioselective pharmacodynamics ofCarprofen andFlunixin‐meglumine in feedlot cattle
Authors: Miciletta M. , Cuniberti B. , Barbero R. , Re G.
Published: April 2013

The activity of the anti‐inflammatory agentsFlunixin‐meglumine (FLU),RS(±)Carprofen (CPF) andS(+)CPFon bovine cyclooxygenases (COXs) has been characterized in feedlot calves using anin vitrowhole blood model. The drugs showed equivalent efficacy in their inhibitory activity onCOXs, and the rank order of potency for bothCOX‐1 andCOX‐2 inhibition wasFLU > S(+)CPF > RS(±)CPF. Our results indicated thatFLUis a nonselective inhibitor of bovineCOXs, whereasRS(±)CPFandS(+)CPFexhibited different degrees of preferential inhibition ofCOX‐2 isoenzyme. The rank order ofIC50COX‐1:IC50COX‐2 potency ratios was in factS(+)CPF(51.882) > RS(±)CPF(13.964) > FLU(0.606), and the calculated percentage inhibition ofCOX‐1 corresponding toCOX‐2 inhibition values comprised between 80% and 95% was comprised between 57.697 and 79.865 forFLU, 33.373 and 51.319 forRS(±)CPF, and 0.230 and 4.622 forS(+)CPF, respectively. These findings are discussed in relation to the prediction of the clinical relevance ofCOXinhibition by the test drugs in cattle.
Occurrence of bottlenose dolphins Tursiops truncatus in natural gas fields of the northwestern Adriatic Sea
Authors: Triossi Francesca , Willis Trevor J. , Pace Daniela S.
Published: April 2013

Common bottlenose dolphins, Tursiops truncatus, were surveyed in offshore gas fields off Ravenna, Italy, between Spring and Autumn, 2001–2005. These visual surveys provide the first density estimates of bottlenose dolphins in the Northwestern Adriatic Sea south of the Po River. Since no study has examined the distribution of bottlenose dolphins relative to gas platforms, when dolphins were encountered, their distance from the nearest gas platform was estimated and behaviour was assessed. Dolphins were sighted on ca. 36% of survey trips, which varied in duration from 1 to 6 h. Group size ranged from 1 to ~50 individuals, with no seasonal trend evident in the likelihood of encounter. Dolphin density was estimated to be approximately 80% higher within 750 m of gas platforms, relative to densities >750 m from platforms, although variability around the estimates was high. From a limited number of behavioural observations, slightly higher frequencies of feeding and milling behaviour were observed closer to gas platforms, whereas dolphins observed further away exhibited higher frequencies of socialising and travelling. Gas platforms are known to provide habitat for demersal fishes and act as aggregation points for pelagic fishes, and these data provide some support for the idea that bottlenose dolphins may utilise gas platforms opportunistically as feeding sites.
Harpacticoid copepod response to epiphyte load variations in Posidonia oceanica (L.) Delile meadows
Authors: Arroyo Nina Larissa , Castejón Inés , Dominguez Marta , Terrados Jorge
Published: April 2013

We conducted a field experiment to assess the response of phytal harpacticoids to nutrient‐driven increases of epiphyte load in Posidonia oceanica meadows. First, we evaluated differences in species richness, diversity and assemblage structure of phytal harpacticoids in P. oceanica meadows with differing epiphyte loads. Secondly, we conducted a field experiment where epiphyte load was increased through an in situ addition of nutrients to the water column and evaluated the responses of the harpacticoid assemblages. We predicted that there would be changes in the harpacticoid assemblages as a result of nutrient‐driven increases of epiphyte load, and that these changes would be of a larger magnitude in meadows of low epiphyte load. Our results show that the harpacticoid fauna (>500 μm) present in P. oceanica meadows in the Bay of Palma comprised taxa which are considered phytal and other less abundant ones previously described as sediment dwellers or commensal on other invertebrate species. Nutrient addition had an overall significant effect on epiphyte biomass and on harpacticoid abundance, diversity and assemblage structure, possibly as a response to the increased resources and habitat complexity provided by epiphytes. The abundance of dominant species at each location was favoured by nutrient addition and in some cases correlated with epiphytic biomass, although never strongly. This may indicate that structural complexity or diversity of the epiphytic cover might be more important than the actual epiphytic biomass for the harpacticoid species investigated. More species‐specific studies are necessary to ascertain this and clarify the relationships between harpacticoids and epiphytes in seagrass meadows. To our knowledge, this is the first account of harpacticoid species associated with P. oceanica leaves and the epiphytic community they harbour in the Mediterranean Sea.
Viscous impedance is an important indicator of abnormal esophageal motility
Authors: Clayton S. B. , Rife C. , Kalbfleisch J. H. , Castell D. O.
Published: April 2013

Background

Non‐obstructive Dysphagia (NOD) is one of the most common symptoms evaluated using esophageal manometry. Although manometry is considered the gold standard, many NOD patients have normal evaluations. Esophageal function testing with combined multichannel intraluminal impedance and esophageal manometry (MII‐EM) is performed using ten 5‐mL swallows of a liquid and a viscous material and provides supplemental information about bolus transit. The aim of this study was to evaluate esophageal function using combined MII‐EM in patients with NOD who had normal evaluations with liquid manometry.

Methods

Multichannel intraluminal impedance and esophageal manometry was performed in consecutive patients presenting for evaluation of NOD. Patients were excluded if any abnormality was detected during liquid manometry. Viscous manometry and liquid and viscous impedance data were analyzed to detect manometric or bolus transit abnormalities. Patients referred for GERD evaluation without any swallowing complaints were used as patient controls and were subject to the same exclusion criteria as the NOD group. All swallow evaluations were performed with 10 liquid and 10 viscous swallows.

Key Results

Data from 240 patients were evaluated, 129 with NOD and 111 patient controls. In the NOD group, 9% (12/129) had abnormal liquid impedance and 29% (37/129) had abnormal viscous impedance. In the control group, 4% (4/111) had abnormal liquid impedance and 16% (18/111) had abnormal viscous impedance. Chi‐square analysis showed a significant difference between the two study groups for viscous impedance (P = 0.02) but not for liquid impedance (P = 0.12).

Conclusions & Inferences

Our data support our belief that a normal liquid manometry with an abnormal viscous impedance analysis in a patient with NOD indicates abnormal esophageal motility. Therefore, viscous impedance should be performed on all patients during the evaluation of NOD.
The glutamate carboxypeptidase AMP1 mediates abscisic acid and abiotic stress responses in Arabidopsis
Authors: Shi Yiting , Wang Zheng , Meng Pei , Tian Siqi , Zhang Xiaoyan , Yang Shuhua
Published: April 2013

ALTERED MERISTEM PROGRAM1 (AMP1) encodes a glutamate carboxypeptidase that plays an important role in shoot apical meristem development and phytohormone homeostasis.

We isolated a new mutant allele of AMP1, amp1‐20, from a screen for abscisic acid (ABA) hypersensitive mutants and characterized the function of AMP1 in plant stress responses.

amp1 mutants displayed ABA hypersensitivity, while overexpression of AMP1 caused ABA insensitivity. Moreover, endogenous ABA concentration was increased in amp1‐20‐ and decreased in AMP1‐overexpressing plants under stress conditions. Application of ABA reduced the AMP1 protein level in plants. Interestingly, amp1 mutants accumulated excess superoxide and displayed hypersensitivity to oxidative stress. The hypersensitivity of amp1 to ABA and oxidative stress was partially rescued by reactive oxygen species (ROS) scavenging agent. Furthermore, amp1 was tolerant to freezing and drought stress. The ABA hypersensitivity and freezing tolerance of amp1 was dependent on ABA signaling. Moreover, amp1 had elevated soluble sugar content and showed hypersensitivity to high concentrations of sugar. By contrast, the contents of amino acids were changed in amp1 mutant compared to the wild‐type.

This study suggests that AMP1 modulates ABA, oxidative and abotic stress responses, and is involved in carbon and amino acid metabolism in Arabidopsis.
Skeletal evidence for variable patterns of handedness in chimpanzees, human hunter–gatherers, and recent British populations
Authors: Stock Jay T. , Shirley Meghan K. , Sarringhaus Lauren A. , Davies Tom G. , Shaw Colin N.
Published: April 2013

Previous studies have shown a strong correspondence between long bone bilateral asymmetry and reported handedness. Here, we compare the pattern of asymmetry in mechanical properties of the humerus and second metacarpal of Pan troglodytes, recent British industrial and medieval populations, and a broad range of human hunter–gatherers, to test whether technological variation corresponds with lateralization in bone function. The results suggest that P. troglodytes are left‐lateralized in the morphology of the humerus and right‐lateralized in the second metacarpal, while all human populations are predominantly right‐biased in the morphology of these bones. Among human populations, the second metacarpals of 63% of hunter–gatherers show right‐hand bias, a frequency similar to that found among chimpanzees. In contrast, the medieval and recent British populations show over 80% right‐lateralization in the second metacarpal. The proportion of individuals displaying right‐directional asymmetry is less than the expected 90% among all human groups. The variation observed suggests that the human pattern of right‐biased asymmetry developed in a mosaic manner throughout human history, perhaps in response to technological development.
Arranged marriage in lipid signalling? The limited choices ofPtdIns(4,5)P2in finding the right partner
Authors: Heilmann M. , Heilmann I.
Published: April 2013

Inositol‐containing phospholipids (phosphoinositides,PIs) control numerous cellular processes in eukaryotic cells. For plants, a key involvement ofPIs has been demonstrated in the regulation of membrane trafficking, cytoskeletal dynamics and in processes mediating the adaptation to changing environmental conditions. Phosphatidylinositol‐4,5‐bisphosphate (PtdIns(4,5)P2) mediates its cellular functionsviabinding to various alternative target proteins. Such downstream targets ofPtdIns(4,5)P2are characterised by the possession of specific lipid‐binding domains, and binding of thePtdIns(4,5)P2ligand exerts effects on their activity or localisation. The large number of potential alternative binding partners – and associated cellular processes – raises the question how alternative or even contrapuntal effects ofPtdIns(4,5)P2are orchestrated to enable cellular function. This article aims to provide an overview of recent insights and new views on how distinct functional pools ofPtdIns(4,5)P2are generated and maintained. The emerging picture suggests thatPtdIns(4,5)P2species containing different fatty acids influence the lateral mobility of the lipids in the membrane, possibly enabling specific interactions ofPtdIns(4,5)P2pools with certain downstream targets.PtdIns(4,5)P2pools with certain functions might also be defined by protein–protein interactions ofPI4P 5‐kinases, which passPtdIns(4,5)P2only to certain downstream partners. Individually or in combination,PtdIns(4,5)P2species and specific protein–protein interactions ofPI4P5‐kinases might contribute to the channelling ofPtdIns(4,5)P2signals towards specific functional effects. The dynamic nature ofPI‐dependent signalling complexes with specific functions is an added challenge for future studies of plantPIsignalling.
Beyond Total Effects: Exploring the Interplay of Personality and Attitudes in Affecting Turnout in the 2009 German Federal Election
Authors: Schoen Harald , Steinbrecher Markus
Published: April 2013

This article addresses the role of personality traits in shaping electoral participation. Utilizing data from a survey conducted after the 2009 German federal election, we demonstrate that agreeableness and emotional stability increase electoral participation. Yet, the main contribution of this article is to link personality traits to attitudinal predictors of turnout. First, we demonstrate that attitudinal variables, including party identification, civic duty, political interest, and internal and external efficacy, serve as intervening variables that mediate the impact of personality on turnout. Second, we show that personality traits exhibit conditioning effects by increasing or decreasing the impact of attitudinal factors on electoral participation. By and large, the evidence suggests that openness, agreeableness, and extraversion render attitudes (somewhat) less powerful in affecting turnout while conscientiousness and emotional stability increase the impact of certain attitudes. Third, we put indirect and conditioning effects together and find that emotional stability and conscientiousness exhibit particularly interesting patterns of effects: They shape attitudes in a way conducive to higher turnout and make these attitudes more powerful in affecting voter participation.
The Effect of Transparency on Trust in Government: A Cross‐National Comparative Experiment
Authors: Grimmelikhuijsen Stephan , Porumbescu Gregory , Hong Boram , Im Tobin
Published: April 2013

Transparency is considered a key value for trustworthy governments. However, the effect of transparency on citizens’ trust across national cultures is overlooked in current research. This article compares the effect of transparency on trust in government in the Netherlands and South Korea. The effect is investigated in two similar series of three experiments. The authors hypothesize that the effect of transparency differs because the countries have different cultural values regarding power distance and short‐ and long‐term orientation. Results reveal similar patterns in both countries: transparency has a subdued and sometimes negative effect on trust in government. However, the negative effect in South Korea is much stronger. The difference in the magnitude of transparency's effect suggests that national cultural values play a significant role in how people perceive and appreciate government transparency.
Collaborative Procurement: A Relational View of Buyer–Buyer Relationships
Authors: Walker Helen , Schotanus Fredo , Bakker Elmer , Harland Christine
Published: April 2013

Collaborative procurement is increasingly on the policy agenda in many countries, yet problems with collaboration occur. This article adopts a relational theory perspective to explore the enablers of and barriers to collaboration in purchasing, helping identify success factors. The authors adopted a mixed qualitative/quantitative methodology and interviewed 51 senior staffers in the United Kingdom. They found that collaborative public procurement is hindered by local politics and differing priorities, supplier resistance, reliance on suppliers for data, and a lack of common coding systems. Enabling factors for collaborating with local governments include dealing with local issues and buying from small and medium‐sized enterprises. For health care providers, important themes are product innovation and ensuring supply. The authors develop a list of enabling factors and show their effect on collaboration success. This may assist policy makers in identifying areas of guidance and help practitioners prevent problems in collaboration.
Spontaneous Recovery of Radial Nerve Function Following Axonamonosis Caused by Impingement from Distal Locking Screws during Humeral Nailing
Authors: Bradley Donal , Arshad Mohammed S. , Aster Asir , Jeyam Muthu
Published: April 2013

A 39-year-old man developed a radial nerve palsy following repair of a left segmental humerus fracture with a rigid interlocking intramedullary nail and screws. His palsy manifested as a wrist and finger drop, associated with numbness in the distribution of the radial nerve. This was managed conservatively with a wrist brace and passive extension exercises. The fracture repair was surgically explored again 9 months later because of a lack of recovery of the radial nerve palsy and fracture non-union leading to localized pressure and pain. During this period, there was no recordable recovery of the nerve; objective clinical assessments were regularly made and the findings were confirmed by neurophysiological studies. During the operation, it was found that the two distal locking screws were impinging on the radial nerve, trapping the epineurium and part of the perineurium. Careful neurolysis was performed and the screws were removed. The fracture was then reduced and fixed without further incident. Immediately following the operation, the patient almost immediately regained complete function in his left wrist and hand. The sensation was restored to normal and the power of his wrist and finger extension returned to Medical Research Council grade 4. As a result of the rapid rate of recovery, we have concluded that impingement by the screws on the patient's radial nerve had resulted in axonamonosis, an uncommon nerve lesion in which pressure on a nerve results in mechanical demyelinization of a length of nerve with interruption of conduction. On release of the pressure, early recovery follows the return of the myelin insulation.
A molecular phylogeny of the checkered beetles and a description of Epiclininae a new subfamily (Coleoptera: Cleroidea: Cleridae)
Authors: GUNTER NICOLE L. , LEAVENGOOD JOHN M. , BARTLETT JUSTIN S. , CHAPMAN ERIC G. , CAMERON STEPHEN L.
Published: April 2013

We provide the first molecular phylogeny of the clerid lineage (Coleoptera: Cleridae, Thanerocleridae) within the superfamily Cleroidea to examine the two most recently proposed hypotheses of higher level classification. Phylogenetic relationships of checkered beetles were inferred from approximately ∼5000 nt of both nuclear and mitochondrial rDNA (28S, 16S and 12S) and the mitochondrial protein‐coding gene COI. A worldwide sample of ∼70 genera representing almost a quarter of generic diversity of the clerid lineage was included and phylogenies were reconstructed using Bayesian and Maximum Likelihood approaches. Results support the monophyly of many proposed subfamilies but were not entirely congruent with either current classification system. The subfamilial relationships within the Cleridae are resolved with support for three main lineages. Tillinae are supported as the sister group to all other subfamilies within the Cleridae, whereas Thaneroclerinae, Korynetinae and a new subfamily formally described here, Epiclininae subf.n., form a sister group to Clerinae + Hydnocerinae.
Identification of a novel HLA‐DQB1*02 variant allele, DQB1*02:01:06
Authors: Heron S. , Ferriola D. , Lind C. , Monos D. S.
Published: April 2013

The new HLA‐DQB1 allele most closely resembles DQB1*02:01:01, differing at a single position 141 (exon 2, codon 15.3).
Correlation between Luminex donor‐specific crossmatches and levels of donor‐specific antibodies in pretransplantation screening
Authors: Guillaume N. , Mazouz H. , Piot V. , Presne C. , Westeel P.‐F.
Published: April 2013

Before kidney transplantation, recipients are routinely screened for preformed antibodies and prospective crossmatches. In this study, we compared prospective Luminex donor‐specific crossmatches (LumXm) with the levels of identified, donor‐specific antibodies (DSAs). LumXm was performed for 108 patient sera, 84 of which were positive for preformed antibodies and 24 of which were negative. Although LumXm can detect class I DSAs (anti‐A and anti‐B) with a mean fluorescence intensity (MFI) as low as 2300, the assay has a ‘grey zone’ for MFIs up to 4000 with a sensitivity of 54% and a specificity of 100%. LumXm can detect a class II DSA (anti‐DRB1) with an MFI as low as 1300 and a sensitivity of 93% and a specificity of 99%. However, these correlations were obtained with two precautions: autocrossmatching and single‐antigen bead assay with denaturing buffer were performed in discordant cases. Moreover, LumXm failed to detect anti‐Cw and anti‐DP in the 10 cases studied. LumXm, therefore, displays certain discrepancies with respect to single‐bead assays – especially for antibodies with a low MFI. Unfortunately, LumXm has a low sensitivity for anti‐A and anti‐B class I antibodies.
Phosphorylation of p27KIP1 homologs KRP6 and 7 by SNF1‐related protein kinase–1 links plant energy homeostasis and cell proliferation
Authors: Guérinier Thomas , Millan Laurine , Crozet Pierre , Oury Céline , Rey François , Valot Benoit , Mathieu Chantal , Vidal Jean , Hodges Michael , Thomas Martine , Glab Nathalie
Published: April 2013

SNF1‐related protein kinase–1 (SnRK1), the plant kinase homolog of mammalian AMP‐activated protein kinase (AMPK), is a sensor that maintains cellular energy homeostasis via control of anabolism/catabolism balance. AMPK‐dependent phosphorylation of p27KIP1 affects cell‐cycle progression, autophagy and apoptosis. Here, we show that SnRK1 phosphorylates the Arabidopsis thaliana cyclin‐dependent kinase inhibitor p27KIP1 homologs AtKRP6 and AtKRP7, thus extending the role of this kinase to regulation of cell‐cycle progression. AtKRP6 and 7 were phosphorylated in vitro by a recombinant activated catalytic subunit of SnRK1 (AtSnRK1α1). Tandem mass spectrometry and site‐specific mutagenesis identified Thr152 and Thr151 as the phosphorylated residues on AtKRP6‐ and AtKRP7, respectively. AtSnRK1 physically interacts with AtKRP6 in the nucleus of transformed BY–2 tobacco protoplasts, but, in contrast to mammals, the AtKRP6 Thr152 phosphorylation state alone did not modify its nuclear localization. Using a heterologous yeast system, consisting of a cdc28 yeast mutant complemented by A. thaliana CDKA;1, cell proliferation was shown to be abolished by AtKRP6WT and by the non‐phosphorylatable form AtKRP6T152A, but not by the phosphorylation‐mimetic form AtKRP6T152D. Moreover, A. thaliana SnRK1α1/KRP6 double over‐expressor plants showed an attenuated AtKRP6‐associated phenotype (strongly serrated leaves and inability to undergo callogenesis). Furthermore, this severe phenotype was not observed in AtKRP6T152D over‐expressor plants. Overall, these results establish that the energy sensor AtSnRK1 plays a cardinal role in the control of cell proliferation in A. thaliana plants through inhibition of AtKRP6 biological function by phosphorylation.
A methyltransferase essential for the methoxypyrazine‐derived flavour of wine
Authors: Dunlevy Jake D. , Dennis Eric G. , Soole Kathleen L. , Perkins Michael V. , Davies Christopher , Boss Paul K.
Published: April 2013

Methoxypyrazines are a family of potent volatile compounds of diverse biological significance. They are used by insects and plants in chemical defence, are present in many vegetables and fruit and, in particular, impart herbaceous/green/vegetal sensory attributes to wines of certain varieties, including Cabernet Sauvignon. While pathways for methoxypyrazine biosynthesis have been postulated, none of the steps have been confirmed genetically. We have used the F2 progeny of a cross between a rapid flowering grapevine dwarf mutant, which does not produce 3‐isobutyl‐2‐methoxypyrazine (IBMP), and Cabernet Sauvignon to identify the major locus responsible for accumulation of IBMP in unripe grape berries. Two candidate methyltransferase genes within the locus were identified and one was significantly associated with berry IBMP levels using association mapping. The enzyme encoded by this gene (VvOMT3) has high affinity for hydroxypyrazine precursors of methoxypyrazines. The gene is not expressed in the fruit of Pinot varieties, which lack IBMP, but is expressed in Cabernet Sauvignon at the time of accumulation of IBMP in the fruit. The results suggest that VvOMT3 is responsible for the final step in methoxypyrazine synthesis in grape berries and is the major determinant of IBMP production.
Acute graft‐versus‐host disease in a nonhematopoietic stem cell transplantation candidate treated with decitabine followed by granulocyte colony‐stimulating factor–primed peripheral blood stem cells infusion: a special entity of the disease?
Authors: Yuan Lei , Sun Lu , Yang Lin , Jing Yu
Published: April 2013

Background

With a well‐developed strategy of acute graft‐versus‐host disease (aGVHD) prophylaxis, the prognosis of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) recipients who develop aGVHD has improved considerably. Meanwhile, transfusion‐associated GVHD (TA‐GVHD) can be fatal. Recent advancements in immune cellular therapy are being adopted in clinical practice, although many concerns including TA‐GVHD remain. This report describes a 64‐year‐old male non‐HSCT candidate diagnosed with acute myeloid leukemia who had received decitabine followed by an infusion of granulocyte–colony‐stimulating factor–primed peripheral blood stem cells (G‐PBSCs) from his daughter, who carried haploidentical human leukocyte antigen. The patient developed aGVHD on the 20th day after infusion.

Study Design and Methods

This study is a single case report of a non‐HSCT candidate who developed skin aGVHD with mild clinical course after decitabine and G‐PBSCs combination. The clinical course, chimerism, and aGVHD pathology studies are detailed.

Results

Compared with conventional aGVHD in allo‐HSCT recipients and TA‐aGVHD, the presentation of this case followed a self‐limited clinical course without marrow aplasia or severe progression. However, the patient eventually died of leukemia without a significant graft‐versus‐leukemia effect.

Conclusion

First, the results demonstrate the existence of aGVHD in elderly non‐HSCT candidates receiving adoptive cellular immune therapy. Second, aGVHD occurring under these conditions is probably a unique entity of aGVHD compared to TA‐aGVHD and the conventional pattern in allo‐HSCT recipients with respect to clinical course and prognosis.
Can family or replacement blood donors become regular volunteer donors?
Authors: Asenso‐Mensah Kwame , Achina Gifty , Appiah Rita , Owusu‐Ofori Shirley , Allain Jean‐Pierre
Published: April 2013

Background

In sub‐Saharan Africa (SSA) confirmed viral marker prevalence between family donors (FDs) and first‐time volunteer nonremunerated donors (VNRDs) is similar. In a blood service collecting 10 units/1000 inhabitants, a questionnaire examined FD donation conditions and willingness of becoming repeat VNRDs.

Study Design and Methods

Four areas were explored: circumstances of visit to hospital, external pressure, experience of donating, and potential repeat donation. After donation and consent, research assistants administered 25 questions and, according to literacy, helped with translation and completion.

Results

Of 513 FDs, three‐fourths were males (median age, 27 years). Only 1.3% were unemployed and more than 50% were students or teachers. Ties with hospitalized patient were family (76%), friends (13%), colleagues, or sharing place of worship (10%). Donating blood was the reason for visiting in 16.8% and 20.9% had previously donated blood probably as FDs. In one‐third of FDs, the family asked for donation of which 10% was pressured by the unjustified reason that not donating was endangering the patient's life. For two‐thirds of FDs, donation was given “because individuals were asked.” Donation was a positive experience for 77% of donors, 62% being interested in predonation testing. Repeating donation was acceptable for 99% of 79% FDs answering.

Discussion

FDs are active in the population, are willing to donate blood if asked, are submitted to little pressure, do not receive incentives, and accept repeat donation. Except for circumstances of donation, FDs are not different from VNRDs and more directly motivated. They constitute a legitimate and important source to improve the blood supply in SSA.
Transfusion of murine red blood cells expressing the human KEL glycoprotein induces clinically significant alloantibodies
Authors: Stowell Sean R. , Girard‐Pierce Kathryn R. , Smith Nicole H. , Henry Kate L. , Arthur C. Maridith , Zimring James C. , Hendrickson Jeanne E.
Published: April 2013

Background

Red blood cell (RBC) alloantibodies to nonself antigens may develop after transfusion or pregnancy, leading to morbidity and mortality in the form of hemolytic transfusion reactions or hemolytic disease of the newborn. A better understanding of the mechanisms of RBC alloantibody induction, or strategies to mitigate the consequences of such antibodies, may ultimately improve transfusion safety. However, such studies are inherently difficult in humans.

Study Design and Methods

We recently generated transgenic mice with RBC‐specific expression of the human KEL glycoprotein, specifically the KEL2 or KEL1 antigens. Herein, we investigate recipient alloimmune responses to transfused RBCs in this system.

Results

Transfusion of RBCs from KEL2 donors into wild‐type recipients (lacking the human KEL protein but expressing the murine KEL ortholog) resulted in dose‐dependent anti‐KEL glycoprotein immunoglobulin (Ig)M and IgG antibody responses, enhanced by recipient inflammation with poly(I:C). Boostable responses were evident upon repeat transfusion, with morbid‐appearing alloimmunized recipients experiencing rapid clearance of transfused KEL2 but not control RBCs. Although KEL1 RBCs were also immunogenic after transfusion into wild‐type recipients, transfusion of KEL1 RBCs into KEL2 recipients or vice versa failed to lead to detectable anti‐KEL1 or anti‐KEL2 responses.

Conclusions

This murine model, with reproducible and clinically significant KEL glycoprotein alloantibody responses, provides a platform for future mechanistic studies of RBC alloantibody induction and consequences. Long‐term translational goals of these studies include improving transfusion safety for at‐risk patients.
Sensitivity of individual‐donation and minipool nucleic acid amplification test options in detecting window period and occult hepatitis B virus infections
Authors: Vermeulen Marion , Coleman Charl , Mitchel Josephine , Reddy Ravi , van Drimmelen Harry , Ficket Tracy , Lelie Nico
Published: April 2013

Background

Several comparison studies showed that the Ultrio assay (Novartis Diagnostics) used in individual‐donation nucleic acid amplification testing (ID‐NAT) format was as sensitive as the TaqScreen assay (Roche) on minipools of six donations (MP6), but the sensitivity of HBV DNA detection has been improved in the new Ultrio Plus version of the assay. A head‐to‐head comparison study was designed to compare the clinical sensitivity of the Ultrio and Ultrio Plus assay in ID, MP4, and MP8 formats using TaqScreen MP6 as a reference assay.

Study Design and Methods

Plasma samples of 107 hepatitis B surface antigen (HBsAg)‐negative, HBV ID‐NAT (Ultrio) positive‐yield samples and 29 HBV DNA–negative, HBsAg‐positive samples were used for comparison of NAT options in replicate testing of dilutions. Viral loads and relative sensitivities were determined by probit analysis against the Eurohep standard.

Results

Ultrio Plus detected a significantly (p < 0.00001) higher proportion of replicate assays on HBV NAT yields (77%) than Ultrio ID (62%) and TaqScreen MP6 (47%), whereas Ultrio Plus MP4 and MP8 detected 53 and 41%, respectively. On HBsAg‐yield samples missed by Ultrio screening, the reactivity rate increased significantly (p < 0.0001) from 23% in Ultrio to 65% in Ultrio Plus and further to 72% (p = 0.10) in the TaqScreen assay. The overall improvement factor of the analytical sensitivity offered by the target enhancer reagent in the Ultrio Plus assay was 2.5 (2.0‐3.1)‐fold on the Ultrio yield samples, but 43 (11‐350)‐fold on the HBsAg yields. In ID‐NAT format the analytical sensitivity of TaqScreen relative to Ultrio Plus was 2.0 (1.0‐4.2), 0.9 (0.7‐1.3), and 1.6 (0.9‐3.0) on the Eurohep standard, HBV NAT–, and HBsAg‐yield samples respectively.

Conclusion

The clinical sensitivity of the currently available commercial NAT methods is mainly driven by the pool size.
A novel method of data analysis for utilization of red blood cell transfusion
Authors: Frank Steven M. , Resar Linda M.S. , Rothschild James A. , Dackiw Elizabeth A. , Savage Will J. , Ness Paul M.
Published: April 2013

Background

A necessary component of an effective blood management program is the accurate and comprehensive collection and analysis of blood utilization data. This study describes innovative methods for analyzing and presenting data for red blood cell (RBC) utilization that compare hemoglobin (Hb) transfusion triggers and targets to those representing the restrictive transfusion strategy advocated by previous large outcome studies.

Study Design and Methods

From one institution, blood utilization data for 134,456 patients, 23,559 of whom were transfused with RBCs, were analyzed. Hb triggers and targets for transfused patients were plotted and graphically compared to the trigger and target ranges from previously published randomized clinical trials.

Results

Nine hospital services with the highest transfusion rates were selected for analysis. The service with the highest Hb trigger and target was further analyzed by comparing transfusion thresholds for individual providers. Differences among services and among individual providers for mean Hb transfusion triggers and targets were significant (up to 1.5 g/dL, p < 0.0001). The variation between the 10th and 90th percentiles for both trigger and target was also significant (up to 3 g/dL, p < 0.0001). If a restrictive transfusion strategy were implemented, the need for transfusion would be reduced or eliminated in 10% to 50% of patients, depending on the service and the individual provider.

Conclusion

By using these methods for analyzing and presenting RBC utilization data, opportunities can be identified for blood conservation, and educational efforts can be directed toward the appropriate individual hospital services and providers.
On the Use of International Commodity Futures Spread for Forecasting China's Net Imports of Commodities
Authors: Chen Tao , Wu Liang , Yan Isabel Kit‐Ming
Published: April 2013

In this paper, we show that the price spreads of copper and aluminium's futures in the London Metal Exchange (LME) and the Shanghai Futures Exchange (SHFE) have strong predictive power of China's net imports of the corresponding commodities 2 months later. The modified Diebold–Mariano test of Harvey et al. (International Journal of Forecasting, 13, 1997, 281) indicates that our futures‐based model significantly outperforms the ARIMA model and static model in terms of 1‐month‐ahead out‐of‐sample forecasts of net imports. Moreover, the market timing test of Clements (Evaluating Econometric Forecasts of Economic and Financial Variables, 2005, Palgrave Macmillan, Xxxxx) indicates that there is a significantly high correlation between the predicted signs of our model and the actual outcomes. When sorting all sign predictions according to the absolute magnitude of the out‐of‐sample movements, our proposed model achieves a 100 per cent forecasting accuracy for both copper and aluminium when predicting the largest movements at the top 10 percentile.
Five observations of a third morphologically distinct feline Demodex mite
Authors: Moriello Karen A. , Newbury Sandra , Steinberg Howard
Published: April 2013

Background

Feline demodicosis is caused by infestation with Demodex cati and/or Demodex gatoi. These two mites have distinctive morphological appearances.

Objectives

To describe five observations of a morphologically distinct feline Demodex mite in 10 cats. All cats were in or adopted from an animal shelter.

Results

A mite with blunted ends longer than D. gatoi but shorter than D. cati was observed in one or multiple cats from animal shelters. Mean mite size was 139 ± 4.5 μm (n = 41 mites). Similar features among the cases included a history of recent recovery or presence of concurrent illness at the time of diagnosis. Pruritus was variable. Hairs were easily epilated in large amounts, and mites were found on either skin scrapings or hair trichograms; mites were most commonly found on the proximal third of hairs examined via trichogram.

Clinical importance

Reports of this mite are uncommon but when present tend to be in cats with concurrent illnesses. Awareness of this mite morphology will hopefully provide other investigators with specimens for molecular testing to determine whether this is a third species or a variant of D. gatoi or D. cati.
Novel protease‐based diagnostic devices for detection of wound infection
Authors: Heinzle Andrea , Papen‐Botterhuis Nicole E. , Schiffer Doris , Schneider Konstantin P. , Binder Barbara , Schintler Michael , Haaksman Ingrid K. , Lenting Herman B. , Gübitz Georg M. , Sigl Eva
Published: April 2013

A gelatinase‐based device for fast detection of wound infection was developed. Collective gelatinolytic activity in infected wounds was 23 times higher (p ≤ 0.001) than in noninfected wounds and blisters according to the clinical and microbiological description of the wounds. Enzyme activities of critical wounds showed 12‐fold elevated enzyme activities compared with noninfected wounds and blisters. Upon incubation of gelatin‐based devices with infected wound fluids, an incubation time of 30 minutes led to a clearly visible dye release. A 32‐fold color increase was measured after 60 minutes. Both matrix metalloproteinases and elastases contributed to collective gelatinolytic enzyme activity as shown by zymography and inhibition experiments. The metalloproteinase inhibitor 1,10‐phenanthroline (targeting matrix metalloproteinases) and the serine protease inhibitor phenylmethlysulfonyl fluoride (targeting human neutrophil elastase) inhibited gelatinolytic activity in infected wound fluid samples by 11–37% and 60–95%, respectively. Staphylococcus aureus and Pseudomonas aeruginosa, both known for gelatinase production, were isolated in infected wound samples.
Topical application of the lectin Artin M accelerates wound healing in rat oral mucosa by enhancing TGF‐β and VEGF production
Authors: Kim Yeon J. , Carvalho Fernanda C. , Souza João A.C. , Gonçalves Pedro C.G. , Nogueira Andressa V.B. , Spolidório Luis C. , Roque‐Barreira Maria C. , Cirelli Joni A.
Published: April 2013

The lectin Artin M has been shown to accelerate the wound‐healing process. The aims of this study were to evaluate the effects of Artin M on wound healing in the palatal mucosa of rats and to investigate the effects of Artin M on transforming growth factor beta (TGF‐β) and vascular endothelial growth factor (VEGF) secretion by rat gingival fibroblasts. A surgical wound was created on the palatal mucosa of 72 rats divided into three groups according to treatment: C—Control (nontreated), A—Artin M gel, and V—Vehicle. Eight animals per group were sacrificed at 3, 5, and 7 days postsurgery for histology, immunohistochemistry and determination of the levels of cytokines, and growth factors. Gingival fibroblasts were incubated with 2.5 μg/mL of Artin M for 24, 48, and 72 hours. The expression of VEGF and TGF‐β was determined by enzyme‐linked immunosorbent assay. Histologically, at day 7, the Artin M group showed earlier reepithelialization, milder inflammatory infiltration, and increased collagen fiber formation, resulting in faster maturation of granular tissue than in the other groups (p < 0.05). Artin M–induced cell proliferation in vivo and promoted a greater expression of TGF‐β and VEGF in both experiments (p < 0.05). Artin M was effective in healing oral mucosa wounds in rats and was associated with increased TGF‐β and VEGF release, cell proliferation, reepithelialization, and collagen deposition and arrangement of fibers.
Insulin resistance impairs cutaneous wound healing in mice
Authors: Otranto Marcela , Nascimento Adriana Paulino do , Monte‐Alto‐Costa Andréa
Published: April 2013

Obesity is associated with significant changes in skin combined with metabolic alterations such as insulin resistance. Our aim was to investigate the effects of insulin resistance induced by a high‐fat diet on cutaneous wound healing. Male C57BL/6 mice were fed standard chow (SC group) or high‐fat chow (HFC group) for 30 weeks. On day 0 (28th week), an excisional wound was performed. After 14 days (30th week), the mice were euthanized. Starting from the 8th week, the HFC group had a higher body weight. The HFC group became intolerant to glucose, resistant to insulin, and presented increased plasma cholesterol and triglyceride levels. The wound area was greater in the HFC group. The inflammatory infiltrate and the amount of “fibroblast‐like” cells increased in superficial regions of the lesions in the HFC group. The collagen fibers were more organized and denser in the SC group. Hydroxyproline levels were lower in the HFC group. The nitric oxide synthase‐2‐positive cells were higher in the HFC group. Lipid peroxidation and protein carbonyl levels were higher in the HFC group. The expression levels of alpha‐smooth muscle actin and transforming growth factor‐β were higher in the HFC group. These findings support the hypothesis that insulin resistance leads to delayed cutaneous wound healing.