bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of chest radiograph scoring to lung weight as a quantitative index of pulmonary edema in organ donors
Authors: Ware Lorraine B. , Neyrinck Arne , O’Neal Hollis R. , Lee Jae Woo , Landeck Megan , Johnson Elizabeth , Calfee Carolyn S. , Matthay Michael A. ,   the California Transplant Donor Network
Published: February 2012

Ware LB, Neyrinck A, O’Neal HR, Lee JW, Landeck M, Johnson E, Calfee CS, Matthay MA and the California Transplant Donor Network. Comparison of chest radiograph scoring to lung weight as a quantitative index of pulmonary edema in organ donors.Abstract:  Quantification of the degree of pulmonary edema in organ donors is useful for assessing the clinical severity of pulmonary edema, determining response to therapy, and as an endpoint for therapeutic trials. Currently, there is no accurate non‐invasive method for assessing the degree of pulmonary edema. We tested the performance of a four‐quadrant chest radiographic scoring system compared to quantification of pulmonary edema by excised lung weight in 84 donors whose lungs were not used for transplantation. Chest radiographs were taken 3.6 ± 3.0 h prior to organ procurement and were scored by two of the authors. Lungs were excised without perfusion and individually weighed. The chest radiographic scoring system had good performance: correlation between total radiographic score and total lung weight of 0.61, p < 0.001. Performance of the scoring system was improved when chest radiographs with atelectasis were excluded (r = 0.79, p < 0.001). The area under the receiver operator characteristic curve for the detection of moderate pulmonary edema (total lung weight >1000 g) was 0.80. This chest radiographic scoring system may potentially be used to assess the clinical severity of pulmonary edema and may be useful as part of the evaluation of donors for suitability for lung transplantation.
A new calorie‐free sugar substitute from the leaf of the stevia plant arrives in the UK
Authors: Boileau A. , Fry J. C. , Murray R. 
Published: February 2012

SummaryStevia‐based sweeteners are beginning to enter the UK market following approval for use in the European Union in late 2011. Intensely sweet compounds, called steviol glycosides, are purified from the leaves of the stevia plant to result in a sweetener of natural origin that is about 200 times as sweet as sucrose. The scientific community has been aware of stevia for more than 100 years, yet the case for safety was not made until after reliable purity specifications were established and research results were available that closed safety gaps to the satisfaction of regulators. In food and beverage formulations, steviol glycosides exhibit characteristic behaviours and successful formulation is dependent upon understanding and managing these attributes. Steviol glycosides are particularly well suited for a variety of beverage and dairy applications, confectionery and several other foods. This is in part caused by steviol glycosides' high degree of stability in food processing. Stevia‐based sweeteners offer exciting potential for use as an innovative solution for calorie and sugar reduction.
Functional variability of the Lr34 durable resistance gene in transgenic wheat
Authors: Risk Joanna M. , Selter Liselotte L. , Krattinger Simon G. , Viccars Libby A. , Richardson Terese M. , Buesing Gabriele , Herren Gerhard , Lagudah Evans S. , Keller Beat 
Published: February 2012

SummaryBreeding for durable disease resistance is challenging, yet essential to improve crops for sustainable agriculture. The wheat Lr34 gene is one of the few cloned, durable resistance genes in plants. It encodes an ATP binding cassette transporter and has been a source of resistance against biotrophic pathogens, such as leaf rust (Puccinina triticina), for over 100 years. As endogenous Lr34 confers quantitative resistance, we wanted to determine the effects of transgenic Lr34 with specific reference to how expression levels affect resistance. Transgenic Lr34 wheat lines were made in two different, susceptible genetic backgrounds. We found that the introduction of the Lr34 resistance allele was sufficient to provide comparable levels of leaf rust resistance as the endogenous Lr34 gene. As with the endogenous gene, we observed resistance in seedlings after cold treatment and in flag leaves of adult plants, as well as Lr34‐associated leaf tip necrosis. The transgene‐based Lr34 resistance did not involve a hypersensitive response, altered callose deposition or up‐regulation of PR genes. Higher expression levels compared to endogenous Lr34 were observed in the transgenic lines both at seedling as well as adult stage and some improvement of resistance was seen in the flag leaf. Interestingly, in one genetic background the transgenic Lr34‐based resistance resulted in improved seedling resistance without cold treatment. These data indicate that functional variability in Lr34‐based resistance can be created using a transgenic approach.
Time‐of‐day effects in arousal: disrupted diurnal cortisol profiles in children with ADHD
Authors: Imeraj Lindita , Antrop Inge , Roeyers Herbert , Swanson James , Deschepper Ellen , Bal Sarah , Deboutte Dirk 
Published: February 2012

Background:  Fluctuations in attention‐deficit hyperactivity disorder (ADHD) symptoms related to regulatory deficits in arousal states are themselves characterized by circadian rhythms. Although cortisol is an important circadian arousal‐related marker, studies focusing on across‐the‐day cortisol variations in ADHD are scarce. There is no study with multiple measurements to take into account interday and intraday variability.Methods:  Salivary cortisol was sampled five times a day (awakening, 30 min after awakening, noon, 4 p.m., 8 p.m.) across five consecutive days in 33 children with ADHD (22 with and 11 without oppositional defiant disorder; ODD) and 33 class‐ and sex‐matched controls (aged 6–12). The cortisol awakening response (increase from awakening to 30 min after awakening) and the diurnal cortisol profile (across‐the‐day variations) were compared for ADHD with ODD (ADHD + ODD) and without ODD (ADHD) subgroups and the control group.Results:  The cortisol awakening response was not significantly different between groups. However, longitudinal analyses to evaluate cortisol profiles across the day revealed a significant Group × Time effect (p < .001). More specifically, compared to each other, the ADHD subgroup showed a flatter slope with relative morning hypo‐arousal and evening hyperarousal, whereas the ADHD + ODD subgroup showed a steeper slope with relative morning hyperarousal and evening hypo‐arousal (p < .001).Conclusions:  Findings support time‐related arousal disruptions in children with ADHD associated with the presence or absence of ODD comorbidity. We recommend research on cortisol in larger samples for a better understanding of arousal mechanisms involved in ADHD not only with and without ODD but also with other comorbidities which may have implications for timing of arousal‐based treatments.
First trimester maternal serum free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein A in pregnancies complicated by diabetes mellitus
Authors: Savvidou MD , Syngelaki A , Muhaisen M , Emelyanenko E , Nicolaides KH 
Published: February 2012

Please cite this paper as: Savvidou M, Syngelaki A, Muhaisen M, Emelyanenko E, Nicolaides K. First trimester maternal serum free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein A in pregnancies complicated by diabetes mellitus. BJOG 2012;119:410–416.Objective  To investigate whether markers of first trimester screening for aneuploidies, including fetal nuchal translucency (NT), maternal serum free β‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein A (PAPP‐A), are altered in women with pre‐existing type‐1 and type‐2 diabetes mellitus, and in women that subsequently develop gestational diabetes mellitus (GDM).Design  Retrospective analysis of prospective combined screening for aneuploidies in singleton pregnancies at 11+0–13+6 weeks of gestation.Setting  Antenatal clinic.Population  Singleton pregnancies at 11+0–13+6 weeks of gestation resulting in the delivery of phenotypically normal neonates. The study included 194 women with type‐1 diabetes, 122 women with type‐2 diabetes, 779 women who developed GDM and 41 007 non‐diabetic controls.Methods  Maternal free β‐hCG and PAPP‐A levels were expressed as multiples of the respective normal median (MoM), and fetal NT was expressed as a difference from the expected median (Δ).Main outcome measures  Comparison of median MoM maternal free β‐hCG and PAPP‐A, and fetal NT, in the four outcome groups.Results  There were no significant differences between the groups in median ΔNT and maternal free β‐hCG MoM. Maternal median PAPP‐A in type‐2 diabetes, compared with the non‐diabetic group, was reduced (0.75 MoM, IQR 0.50–1.09 MoM versus 1.00 MoM, IQR 0.68–1.42 MoM; P < 0.001), which resulted in doubling in the false‐positive rate in the combined screening in this population. There were no significant differences in maternal PAPP‐A between the other groups.Conclusions  In women with type‐2 diabetes, the estimation of accurate patient‐specific risk in the first trimester combined screening for aneuploidies necessitates an adjustment of maternal serum PAPP‐A.
Activation of transient receptor potential A1 by a non‐pungent capsaicin‐like compound, capsiate
Authors: Shintaku Kenji , Uchida Kunitoshi , Suzuki Yoshiro , Zhou Yiming , Fushiki Tohru , Watanabe Tatsuo , Yazawa Susumu , Tominaga Makoto 
Published: February 2012

BACKGROUND AND PURPOSE Capsiate is produced by ‘CH‐19 Sweet’ (Capsicum annuun L.), a non‐pungent cultivar of red pepper. Like capsaicin, capsiate is thought to enhance energy metabolism by activating the sympathetic nervous system and suppressing inflammation, but the underlying mechanisms for this are uncertain. We previously reported that capsiate could activate transient receptor potential vanilloid 1 (TRPV1), a capsaicin receptor. The purpose of the present study is to investigate whether capsinoids activate other TRP channels.EXPERIMENTAL APPROACH Using Ca2+ imaging and whole‐cell patch‐clamp methods, we analysed the response of TRP channels to three kinds of capsinoids, capsiate, dihydrocapsiate and nordihydrocapsiate, in HEK293T cells expressing TRP channels or in primary cultures of mouse dorsal root ganglion neurons.KEY RESULTS We found that in both cell types TRP ankyrin 1 (TRPA1) had a slightly weaker response to capsinoids compared with TRPV1, with the capsiate EC50 for TRPA1 activation being more than that for TRPV1 activation, and that the capsinoid‐evoked action was blocked by a specific TRPA1 antagonist. TRPA1 was activated by capsinoids, but not by their degradation products. Amino acids known to participate in TRPA1 activation following cysteine covalent modification or zinc treatment were not involved in the activation of TRPA1 by capsinoid.CONCLUSIONS AND IMPLICATIONS Taken together, these results indicate that capsinoids activate TRPA1 by an as yet unknown mechanism, and TRPA1 could be involved in physiological phenomena associated with capsinoid treatment.
A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts
Authors: Swarnkar Gaurav , Sharan Kunal , Siddiqui Jawed A , Mishra Jay Sharan , Khan Kainat , Khan Mohd Parvez , Gupta Varsha , Rawat Preeti , Maurya Rakesh , Dwivedi Anil K , Sanyal Sabyasachi , Chattopadhyay Naibedya 
Published: February 2012

BACKGROUND AND PURPOSE Naringenin and its derivatives have been assessed in bone health for their oestrogen‐‘like’ effects but low bioavailability impedes clinical potential. This study was aimed at finding a potent form of naringenin with osteogenic action.EXPERIMENTAL APPROACH Osteoblast cultures were harvested from mouse calvaria to study differentiation by naringenin, isosakuranetin, poncirin, phloretin and naringenin‐6‐C‐glucoside (NCG). Balb/cByJ ovariectomized (OVx) mice without or with osteopenia were given naringenin, NCG, 17β‐oestradiol (E2) or parathyroid hormone (PTH). Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labelling of bone. Plasma levels of NCG and naringenin were determined by HPLC.KEY RESULTS NCG stimulated osteoblast differentiation more potently than naringenin, while isosakuranetin, poncirin or phloretin had no effect. NCG had better oral bioavailability than naringenin. NCG increased the mRNA levels of oestrogen receptors (ERs) and bone morphogenetic protein (an ER responsive gene) in vivo, more than naringenin. In OVx mice, NCG treatment in a preventive protocol increased bone formation rate (BFR) and improved trabecular microarchitecture more than naringenin or E2. In osteopenic mice, NCG but not naringenin, in a therapeutic protocol, increased BFR and improved trabecular microarchitecture, comparable with effects of PTH treatment. Stimulatory effects of NCG on osteoblasts were abolished by an ER antagonist. NCG transactivated ERβ but not ERα. NCG exhibited no uterine oestrogenicity unlike naringenin.CONCLUSIONS AND IMPLICATIONS NCG is a potent derivative of naringenin that has bone anabolic action through the activation of osteoblast ERs and exhibited substantial oral bioavailability.
Agonist‐dependent modulation of arterial endothelinA receptor function
Authors: Compeer MG , Meens MJPMT , Hackeng TM , Neugebauer WA , Höltke C , De Mey JGR 
Published: February 2012

BACKGROUND AND PURPOSE Endothelin‐1 (ET‐1) causes long‐lasting vasoconstrictions. These can be prevented by ETA receptor antagonists but are only poorly reversed by these drugs. We tested the hypothesis that endothelin ETA receptors are susceptible to allosteric modulation by endogenous agonists and exogenous ligands.EXPERIMENTAL APPROACH Rat isolated mesenteric resistance arteries were pretreated with capsaicin and studied in wire myographs, in the presence of L‐NAME and indomethacin to concentrate on arterial smooth muscle responses.KEY RESULTS Endothelins caused contractions with equal maximum but differing potency (ET‐1 = ET‐2 > ET‐3). ET‐11–15 neither mimicked nor antagonized these effects in the absence and presence of ET16–21. 4AlaET‐1 (ETB agonist) and BQ788 (ETB antagonist) were without effects. BQ123 (peptide ETA antagonist) reduced the sensitivity and relaxed the contractile responses to endothelins. Both effects depended on the agonist (pKB: ET‐3 = ET‐1 > ET‐2; % relaxation: ET‐3 = ET‐2 > ET‐1). Also, with PD156707 (non‐peptide ETA antagonist) agonist‐dependence and a discrepancy between preventive and inhibitory effects were observed. The latter was even more marked with bulky analogues of BQ123 and PD156707.CONCLUSIONS AND IMPLICATIONS These findings indicate allosteric modulation of arterial smooth muscle ETA receptor function by endogenous agonists and by exogenous endothelin receptor antagonists. This may have consequences for the diagnosis and pharmacotherapy of diseases involving endothelins.
Functional efficacy of adenosine A2A receptor agonists is positively correlated to their receptor residence time
Authors: Guo Dong , Mulder‐Krieger Thea , IJzerman Adriaan P , Heitman Laura H 
Published: February 2012

BACKGROUND AND PURPOSE The adenosine A2A receptor belongs to the superfamily of GPCRs and is a promising therapeutic target. Traditionally, the discovery of novel agents for the A2A receptor has been guided by their affinity for the receptor. This parameter is determined under equilibrium conditions, largely ignoring the kinetic aspects of the ligand‐receptor interaction. The aim of this study was to assess the binding kinetics of A2A receptor agonists and explore a possible relationship with their functional efficacy.EXPERIMENTAL APPROACH We set up, validated and optimized a kinetic radioligand binding assay (a so‐called competition association assay) at the A2A receptor from which the binding kinetics of unlabelled ligands were determined. Subsequently, functional efficacies of A2A receptor agonists were determined in two different assays: a novel label‐free impedance‐based assay and a more traditional cAMP determination.KEY RESULTS A simplified competition association assay yielded an accurate determination of the association and dissociation rates of unlabelled A2A receptor ligands at their receptor. A correlation was observed between the receptor residence time of A2A receptor agonists and their intrinsic efficacies in both functional assays. The affinity of A2A receptor agonists was not correlated to their functional efficacy.CONCLUSIONS AND IMPLICATIONS This study indicates that the molecular basis of different agonist efficacies at the A2A receptor lies within their different residence times at this receptor.
Characterization of novel RHD alleles: relationship between phenotype, genotype, and trimeric architecture
Authors: Silvy Monique , Chapel‐Fernandes Sylvie , Callebaut Isabelle , Beley Sophie , Durousseau Cécile , Simon Sophie , Lauroua Pierre , Dubosc‐Marchenay Nadine , Babault Catherine , Mouchet Chantal , Ferrera Virginie , Chiaroni Jacques , Bailly Pascal 
Published: February 2012

BACKGROUND: RH1 is one of the most clinically important blood group antigens in the field of transfusion and prevention of fetomaternal incompatibilities. New variant RHD alleles are regularly identified and their characterization is essential to ensuring patient safety.STUDY DESIGN AND METHODS: Blood samples with uncertain RhD phenotypes not resolved by our first‐line SNaPshot assay were sequenced for all 10 RHD exons. RHD zygosity was investigated. Flow cytometry was performed to determine RhD antigen density and epitope pattern.RESULTS: Seven novel RHD alleles were identified. Six, that is, RHD(T55P), RHD(A85G), RHD(G132R), RHD(G132E), RHD(D403V), and DAR(T203A), resulted from nucleotide polymorphisms. The seventh, that is, RHD(S182WfsX46), resulted from a 4‐bp deletion that led to a reading frame shift and the appearance of a premature stop codon. Study of RhD expression of the first five alleles at hemizygous state showed greatly reduced antigen densities ranging from 50 to 618 antigens per red blood cell (RBC). DAR(T203A) was classified as a partial D antigen with a weakened reactivity profile similar to that of DAR. As expected, no D antigen was detected on RBCs carrying the RHD(S182WfsX46) allele. In parallel, RhD expression of RHD(G336R)/weak D type 58, RHD(F410V), and suspected RHD(1‐9)‐CE was determined to be less than or equal to 50 antigens per RBC. RhAG/RhD2 trimer model supports the observed phenotypes.CONCLUSION: Although the frequency of the new RHD alleles presented herein is low, their phenotypic and genotypic description adds to the repertoire of reported RHD alleles. These data can be useful for optimization of molecular screening tools.
Cryopreservation of umbilical cord blood with a novel freezing solution that mimics intracellular ionic composition
Authors: Nicoud Ian B. , Clarke Dominic M. , Taber Greta , Stolowski Kristin M. , Roberge Sarah E. , Song Melissa K. , Mathew Aby J. , Reems Jo‐Anna 
Published: February 2012

BACKGROUND: Cryopreservation protocols have remained relatively unchanged since the first umbilical cord blood banking program was established. This study evaluated the preservation efficacy of a novel intracellular‐like cryopreservation solution (CryoStor, BioLife Solutions, Inc.), the rate of addition of two cryopreservation solutions to cord blood units (CBUs), and reduced final dimethyl sulfoxide (DMSO) concentration of 5%.STUDY DESIGN AND METHODS: Split‐sample CBUs were cryopreserved with either an in‐house 20% DMSO‐based cryopreservation solution or CryoStor CS10 at a rate of 1 mL/min (n = 10; i.e., slow addition) or as a bolus injection (n = 6; i.e., fast addition). Infrared images of exothermic effects of the cryopreservation solutions were monitored relative to the rate of addition. Prefreeze and postthaw colony‐forming unit assays, total nucleated cells, and CD34+ cell counts were compared.RESULTS: Maximum temperature excursions observed were less than 6°C, regardless of the rate of solution addition. Fast addition resulted in peak excursions approximately twice that of slow addition but the magnitude and duration were minimal and transient. Slow addition of CryoStor CS10 (i.e., final concentration ≤5% DMSO) resulted in significantly better postthaw CD34+ cell recoveries; no other metrics were significantly different. Fast addition of CryoStor resulted in similar postthaw metrics compared to slow addition of the in‐house solution.CONCLUSION: Slow and fast addition of cryopreservation solutions result in mean temperature changes of approximately 3.3 to 4.45°C. Postthaw recoveries with CryoStor were equivalent to or slightly better than with the in‐house cryopreservation solution. CryoStor also provides several advantages including reduced processing time, formulation consistency, and reduced DMSO in the frozen product (≤5%).
Distinct overlapping sequences at the carboxy‐terminus of merlin regulate its tumour suppressor and morphogenic activity
Authors: Laulajainen Minja , Melikova Maria , Muranen Taru , Carpén Olli , Grönholm Mikaela 
Published: February 2012

AbstractThe Neurofibromatosis 2 (NF2)gene product merlin is a tumour suppressor, which in addition to inhibiting cell proliferation regulates cell morphology. The morphogenic properties of merlin may play a role in tumour suppression, as patient‐derived tumour cells demonstrate cytoskeletal abnormalities. However, it is still unclear how these functions are linked. The N‐terminalFERM‐domain of merlin is highly homologous to the oncogenic protein ezrin, while the C‐termini are less conserved, suggesting that the opposite effect of the proteins on proliferation could be mediated by their distinct C‐terminal regions. In this study we characterize the role of the most C‐terminal residues of merlin in the regulation of proliferation, cytoskeletal organization, phosphorylation and intramolecular associations. In addition to the two full‐length merlin isoforms and truncating mutations found in patients, we focused on the evolutionally conserved C‐terminal residues 545‐547, also harbouring disease‐causing mutations. We demonstrate that merlin induces cell extensions, which result from impaired retraction of protrusions rather than from increased formation of filopodia. The residues 538‐568 were found particularly important for this morphogenic activity. The results further show that both merlin isoforms are able to equally inhibit proliferation, whereas C‐terminal mutants affecting residues 545‐547 are less effective in growth suppression. This study demonstrates that the C‐terminus contains distinct but overlapping functional domains important for regulation of the morphogenic activity, intramolecular associations and cell proliferation.
An ATP‐driven potassium pump promotes long‐term survival of Halobacterium salinarum within salt crystals
Authors: Kixmüller Dorthe , Greie Jörg‐Christian 
Published: February 2012

SummaryMany extremely halophilic archaea belonging to the Halobacteriales have remarkable longevity. They are even known to persist for millions of years within fluid inclusions of salt crystals. However, the key systems responsible for this remarkable ability and the underlying physiological mechanisms have not yet been deciphered. This study revealed that the ATP‐dependent K+ uptake system KdpFABC of Halobacterium salinarum is essential for survival under desiccation and salt crystal inclusion and, thus, can be identified as at least one of these systems in this organism. The presence of the kdp genes promoted survival of H. salinarum entombed in halite, compared with cells in which these genes were deleted. Expression of the kdp operon was found to be induced already under desiccating conditions without halite entombment. The morphology of cells included in halite resembled that of cells grown under potassium limitation. Therefore, a steady potassium supply, even under unfavourable energetic conditions, plays a key role in long‐term survival and desiccation tolerance.