bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogeography of Ramalina menziesii, a widely distributed lichen‐forming fungus in western North America
Authors: Sork Victoria L. , Werth Silke 
Published: March 2014

AbstractThe complex topography and climate history of western North America offer a setting where lineage formation, accumulation and migration have led to elevated inter‐ and intraspecific biodiversity in many taxa. Here, we study Ramalina menziesii, an epiphytic lichenized fungus with a range encompassing major ecosystems from Baja California to Alaska to explore the predictions of two hypotheses: (i) that the widespread distribution of R. menziesii is due to a single migration episode from a single lineage and (ii) that the widespread distribution is due to the formation and persistence of multiple lineages structured throughout the species' range. To obtain evidence for these predictions, we first construct a phylogenetic tree and identify multiple lineages structured throughout the species' range – some ancient ones that are localized and other more recent lineages that are widely distributed. Second, we use an isolation with migration model to show that sets of ecoregion populations diverged from each other at different times, demonstrating the importance of historical and current barriers to gene flow. Third, we estimated migration rates among ecoregions and find that Baja California populations are relatively isolated, that inland California ecoregion populations do not send out emigrants and that migration out of California coastal and Pacific Northwest populations into inland California ecoregions is high. Such intraspecific geographical patterns of population persistence and dispersal both contribute to the wide range of this genetically diverse lichen fungus and provide insight into the evolutionary processes that enhance species diversity of the California Floristic Province.
Caffeine stabilizes Cdc25 independently of Rad3 in Schizosaccharomyces pombe contributing to checkpoint override
Authors: Alao John P. , Sjölander Johanna J. , Baar Juliane , Özbaki‐Yagan Nejla , Kakoschky Bianca , Sunnerhagen Per 
Published: March 2014

SummaryCdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3‐dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3‐related proteins in both Schizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S. pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA‐damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S. pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine‐induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25.
Adaptive parental effects: the importance of estimating environmental predictability and offspring fitness appropriately
Authors: Burgess Scott C. , Marshall Dustin J. 
Published: March 2014

Anticipatory parental effects (APE's) occur when parents adjust the phenotype of their offspring to match the local environment, so as to increase the fitness of both parents and offspring. APE's, as in the evolution of adaptive phenotypic plasticity more generally, are predicated on the idea that the parental environment is a reliable predictor of the offspring environment. Most studies on APE's fail to explicitly consider environmental predictability so risk searching for APE's under circumstances where they are unlikely to occur. This failure is perhaps one of the major reasons for mixed evidence for APE's in a recent meta‐analysis. Here, we highlight some often‐overlooked assumptions in studies of APE's and provide a framework for identifying and testing APE's. Our review highlights the importance of measuring environmental predictability, outlines the minimal requirements for experimental designs, explains the important differences between relative and absolute measures of offspring fitness, and highlights some potential issues in assigning components of offspring fitness to parental fitness. Our recommendations should result in more targeted and effective tests of APE's.SynthesisA decent set of theory is available to understand when certain kinds of parental effects might act to increase parental fitness (i.e. be ‘adaptive’). This theory could be better incorporated into empirical studies on anticipatory parental effects (APE's). Here, we provide practical advice for how empirical studies can more closely align with the theoretical underpinnings of adaptive parental effects. In short, robust inferences on APE's require quantitative estimates of environmental predictability in the field over the space and time scales relevant to the life history of the study organism as well as an understanding of when to use absolute or relative offspring fitness.
Significance of Repeat Programmed Ventricular Stimulation at Electrophysiology Study for Arrhythmia Prediction after Acute Myocardial Infarction
Authors: ZAMAN SARAH , NARAYAN ARUN , THIAGALINGAM ARAVINDA , SIVAGANGABALAN GOPAL , THOMAS STUART , ROSS DAVID L. , KOVOOR PRAMESH 
Published: March 2014

BackgroundThe prognostic significance of a second programmed ventricular stimulation (PVS) at electrophysiology study (EPS), when the first PVS is negative for inducible ventricular tachycardia (VT), in patients following myocardial infarction (MI) is unknown.MethodsConsecutive ST‐elevation MI patients with left ventricular ejection fraction ≤40% following revascularization underwent early EPS. An implantable cardioverter defibrillator (ICD) was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible ventricular fibrillation [VF]/flutter) EPS. The combined primary end point of death or arrhythmia (sudden death, resuscitated cardiac arrest, and spontaneous VT/VF) was assessed in EPS‐positive patients grouped according to if VT was induced on the first PVS application, or the second PVS application, when the first was negative.ResultsEPS performed a median 8 days post‐MI in 290 patients was negative in 70% (n = 203) and positive in 30% (n = 87). In patients with a positive EPS, VT was induced on the first PVS in 67% (n = 58) and the second PVS, after the first was negative, in 33% (n = 29). Predischarge ICD was implanted in 79 of 87 patients with a positive EPS. Three‐year primary end point occurred in 20.9 ± 5.6% and 38.3 ± 9.7% of patients with VT induced by the first and second PVS, respectively (P = 0.042) and in 6.3 ± 1.9% of electrophysiology‐negative patients (P < 0.001).ConclusionsIn patients with post‐MI left ventricular dysfunction, VT can be induced in a significant proportion with a second PVS when negative on the first. These patients have a similar higher risk of death or arrhythmia compared to patients with VT induced on the first PVS.
The pharmacokinetics of methadone and its metabolites in neonates, infants, and children
Authors: Ward Robert M. , Drover David R. , Hammer Gregory B. , Stemland Christopher J. , Kern Steve , Tristani‐Firouzi Martin , Lugo Ralph A. , Satterfield Kristin , Anderson Brian J. 
Published: March 2014

SummaryBackgroundThe lack of methadone pharmacokinetic data in children and neonates restrains dosing to achieve the target concentration in these populations. A minimum effective analgesic concentration of methadone in opioid naïve adults is 0.058 mg·l−1, while no withdrawal symptoms were observed in neonates suffering opioid withdrawal if plasma concentrations of methadone were above 0.06 mg·l−1. The racemate of methadone which is commonly used in pediatric and anesthetic care is metabolized to 2‐ethylidine‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP) and 2‐ethyl‐5‐methyl‐3,3‐diphenylpyrroline (EMDP).MethodsData from four studies (age 33‐week PMA‐15 years) were pooled (n = 56) for compartment analysis using nonlinear mixed effects modeling. Parameter estimates were standardized to a 70‐kg person using an allometric model approach. Investigation was made of the racemate and metabolite (EDDP and EMDP) dispositions. In addition, neonatal data (n = 7) allowed further study of R‐ and S‐enantiomer pharmacokinetics.ResultsA three‐compartment linear disposition model best described the observed time–concentration profiles with additional compartments for metabolites. Population parameter estimates (between‐subject variability) were central volume (V1) 21.5 (29%) l·70 kg−1, peripheral volumes of distribution V2 75.1 (23%) l·70 kg−1 and V3 484 (8%) l·70 kg−1, clearance (CL) 9.45 (11%)l·h−1·70 kg−1, and intercompartment clearances Q2 325 (21%) l·h−1·70 kg−1 and Q3 136 (14%) l·h−1·70 kg−1. EDDP formation clearance was 9.1 (11%) l·h−1·70 kg−1, formation clearance of EMDP from EDDP 7.4 (63%)l·h−1·70 kg−1, elimination clearance of EDDP was 40.9 (26%) l·h−1·70 kg−1 and the rate constant for intermediate compartments 2.17 (43%) h−1.ConclusionsCurrent pharmacokinetic parameter estimates in children and neonates are similar to those reported in adults. There was no clearance maturation with age. Neonatal enantiomer clearances were similar to those described in adults. A regimen of 0.2 mg·kg−1 per 8 h in neonates achieves a target concentration of 0.06 mg·l−1 within 36 h. Infusion, rather than intermittent dosing, should be considered if this target is to be achieved in older children after cardiac surgery.
The effect of fentanyl and clonidine on early postoperative negative behavior in children: a double‐blind placebo controlled trial
Authors: Bortone Luciano , Bertolizio Gianluca , Engelhardt Thomas , Frawley Geoff , Somaini Marta , Ingelmo Pablo M. 
Published: March 2014

SummaryBackgroundEarly negative postoperative behavior (e‐PONB) is common in children and manifests itself as emergence agitation (EA), emergence delirium (ED), and pain. The objective of this prospective double blind, randomized, placebo‐controlled trial was to determine whether IV clonidine or IV fentanyl prior to surgery modifies e‐PONB in children.MethodsNinety children scheduled for subumbilical surgery under sevoflurane anesthesia supplemented with regional anesthesia were randomized to either receive IV clonidine 2 mcg·kg−1, IV fentanyl 2 mcg·kg−1 or placebo (IV saline) before surgery. Primary outcome measures were the incidence of EA, ED and pain during the first hour after awakening. Secondary outcome measures were side effects such as nausea and vomiting and delayed discharge from PACU.ResultsEighty‐seven children (n = 29 per group) completed the study. EA was present in 10 children (six clonidine, none fentanyl, and four placebo, P = 0.04) whereas ED was observed in 20 children (nine clonidine, three fentanyl, and eight placebo P = 0.13). Sixteen children who received placebo had a CHIPPS score of ≥4 compared with nine children in fentanyl group and 18 children receiving clonidine (P = 0.04). Ten children receiving fentanyl vomited during the first postoperative day, compared with six children in placebo group and none in clonidine group (P = 0.003). Discharge from PACU was not affected.ConclusionsIV fentanyl before surgery but not IV clonidine modifies e‐PONB in children undergoing lower abdominal surgery under general anesthesia supplemented with regional anesthesia. The use of fentanyl in this population was also associated with reduced pain scores after awakening but with significantly greater incidence of PONV.
Transient abdominal wall deformity in an infant Blaming the caudal?
Authors: Tosetti Sylvain , Frigon Chantal 
Published: March 2014

SummaryLocoregional anesthesia is an important aspect of perioperative analgesia. It decreases requirements for anesthetic agents and opioids, decreases the surgical stress response, and provides postoperative analgesia. Nonetheless, pediatric patients, especially infants, demonstrate specificities towards regional anesthesia techniques, as an increased sensitivity to local anesthetics (LA) and a higher ease of LA spread especially when using blocks that rely on the volume of LA and its spread as those used for abdominal wall analgesia or caudal. Thus, we present a case of transient abdominal wall deformity following caudal anesthesia in an infant.
Chlorin e6 Derivative Radachlorin Mainly Accumulates in Mitochondria, Lysosome and Endoplasmic Reticulum and Shows High Affinity toward Tumors in Nude Mice in Photodynamic Therapy
Authors: Biswas Raktim , Moon Jeong Hwan , Ahn Jin‐Chul 
Published: March 2014

AbstractThe efficacy of photodynamic therapy (PDT) depends upon the amount of photosensitizer accumulated in the malignant tissues. Radachlorin is a popular photosensitizer used in photodynamic therapy to treat various types of cancer. In this study, we have studied the main organelles responsible for the accumulation of radachlorin in human anaplastic thyroid cancer in vitro and in vivo. The optimal time window for uptake and clearance of radachlorin also was studied. Confocal microscopic images confirmed that the radachlorin is mainly acquired by mitochondria and partially by lysosome and endoplasmic reticulum. Studies also showed that the maximum amount of radachlorin was accumulated within 3–6 h after the treatment. Radachlorin also showed a higher affinity toward malignant tumors compared to the other organs in mice xenograft model. Uptake of radachlorin reached an optimum amount within 6 h and most of the radachlorins were also cleared from the body in next 48 h. Therefore, detailed information regarding exact accumulation sites and a time window in which maximum amount of drug is accumulated and cleared were obtained by this study. Hence, not only the efficacy of the treatment can be increased but the phototoxicity after the treatment also can be controlled.
A Lotus japonicus mutant defective in nitrate uptake is also affected in the nitrate response to nodulation
Authors: Pal'ove‐Balang P. , García‐Calderón M. , Pérez‐Delgado C. M. , Pavlovkin J. , Betti M. , Márquez A. J. 
Published: March 2014

AbstractA chlorate‐resistant mutant (Ljclo1) of the model legume Lotus japonicus was identified that showed normal levels of nitrate reductase enzyme activity but had decreased uptake of nitrate, as determined from nitrate depletion and electrophysiological measurements. The data suggest that the mutant could be affected specifically in the low‐affinity but not in the high‐affinity nitrate transport system, and also showed decreased uptake of chlorate. Back‐crosses of the mutant plant to the wild type indicated that it is affected in a single Mendelian recessive trait. Thus, the mutation produced in Ljclo1 may be related to some of the low‐affinity nitrate transporters or to a regulatory mechanism associated with nitrate/chlorate uptake. Both size and chlorophyll content in young leaves of the mutant plants were significantly reduced compared to the wild type. In addition, nodulation performance of the mutant plants was similar to the wild type in the absence of any exogenous nitrate. However, the nodule:root biomass ratio in mutant plants was considerably reduced in the presence of 1–2 mm nitrate. The levels of several transcripts for nitrate transport and assimilation genes were determined for the wild type and mutant plants and were slightly different. The results suggest interdependence between nitrate uptake, plant growth and nodulation in Ljclo1 mutant plants.
Comparison of the modified shuttle walk test and cardiopulmonary exercise test in sarcoidosis
Authors: de Boer Sally , Kolbe John , Wilsher Margaret L. 
Published: March 2014

AbstractBackground and objectiveDyspnoea and exercise intolerance are common in sarcoidosis and are often poorly correlated with resting lung function. Measurement of peak exercise capacity is likely to be helpful in assessing and monitoring disease. The aim of this study was to compare the modified shuttle walk test (MSWT) to cardiopulmonary exercise test (CPET) as a measure of peak exercise capacity in sarcoidosis.MethodsThirty‐three (17 male, mean age 48 years) patients with sarcoidosis completed a standardized exponential exercise protocol cycle ergometer CPET and a single corridor MSWT in random order.ResultsSubjects has a mean forced expiratory volume in 1 s (FEV1) 2.4 L (75.7%predicted), forced vital capacity (FVC) 3.43 L (88.7%predicted) and diffusing capacity for carbon monoxide (DLCO) 20.3 mL/min/mm Hg (71.4%predicted). There was a strong correlation between MSWT distance and peak oxygen uptake (VO2) during CPET (r = 0.87; P < 0.0001), and between maximum heart rate during MSWT and CPET (r = 0.82; P < 0.0001). There was a moderate correlation between FEV1, FVC and DLCO with MSWT distance (r = 0.55, r = 0.61, r = 0.61, respectively; all P < 0.001) and with peak VO2 (r = 0.62, r = 0.63, r = 0.62, respectively; all P < 0.0001).ConclusionsPeak VO2 achieved during CPET strongly correlated with MSWT distance. MSWT is a measure of peak exercise capacity in sarcoidosis that does not require equipment and can be readily available in the clinic.
Genomic full‐length sequence of two novel HLA‐DRB1 alleles, DRB1*15:01:01:03 and DRB1*15:01:01:04, identified by cloning and sequencing
Authors: Lu L. , Xu Y. P. 
Published: March 2014

AbstractTwo novel alleles, HLADRB1*15:01:01:03 and DRB1*15:01:01:04, identified in two Chinese donors.
Reduced residual gene expression of nuclear factor of activated T cells‐regulated genes correlates with the risk of cytomegalovirus infection after liver transplantation
Authors: Steinebrunner N. , Sandig C. , Sommerer C. , Hinz U. , Giese T. , Stremmel W. , Zahn A. 
Published: March 2014

AbstractBackgroundPharmacokinetic monitoring of calcineurin inhibitors (CNIs) is unsatisfactory because, at comparable blood concentrations, side effects vary considerably. We recently confirmed the applicability of a pharmacodynamic (PD) assay that measures the suppression of CNI target genes, specifically the suppression of nuclear factor of activated T cells (NFAT)‐regulated genes in liver transplant (LT) recipients. The aim of this prospective study was to prove the clinical reliability of this assay. Therefore, we quantified the residual gene expression (RGE) of NFAT‐regulated genes and evaluated the association between the RGE of NFAT‐regulated genes and the incidence of cytomegalovirus (CMV) infection.Patients and methodsIn 20 LT recipients, 10 patients on cyclosporine (CsA) and 10 patients on tacrolimus (Tac) therapy, who presented with CMV infection, the RGEs of interleukin‐2, interferon‐γ (IFNγ), and granulocyte–monocyte colony‐stimulating factor were measured and compared with the RGEs of these cytokines in 40 healthy dose‐matched LT controls.ResultsCsA‐treated CMV patients demonstrated a lower RGE of all NFAT‐regulated genes compared with controls (30 ± 17 vs. 44 ± 20, P = 0.067). For IFNγ, the level of significance was reached (26 ± 17 vs. 43 ± 17, P = 0.0125). Daily CsA dosage, CsA baseline (C0) and 2 h (C2) concentrations were comparable (CsA dosage 169 mg/day vs. 165 mg/day; CsA C0 94 μg/L vs. 85 μg/L; CsA C2 389 μg/L vs. 381 μg/L). In addition, Tac‐treated CMV patients demonstrated a lower RGE of all NFAT‐regulated genes compared with controls (68 ± 25 vs. 84 ± 22, P = 0.0769). Analogous to CsA‐treated CMV patients, the level of significance was reached for IFNγ (61 ± 24 vs. 88 ± 29, P = 0.0154). Daily Tac dosage and Tac 1.5 h concentrations (C1.5) were comparable in both groups (Tac dosage 4 mg/day vs. 4 mg/day; Tac C1.5 8 μg/L vs. 10 μg/L), whereas Tac C0 concentrations were significantly higher in controls (Tac C0 4 μg/L vs. 6 μg/L, P = 0.0276).ConclusionMeasuring the RGE of NFAT‐regulated genes is appropriate to assess the risk of infections in LT recipients. Measuring the RGE of IFNγ is particularly suitable to assess the risk of CMV infection. PD monitoring of CNIs in LT recipients is an approach to individualize immunosuppression, which may help to reduce infectious complications.
Log canonical pairs with good augmented base loci
Authors: Birkar Caucher , Hu Zhengyu 
Published: March 2014

AbstractLet $(X,B)$ be a projective log canonical pair such that $B$ is a $\mathbb{Q}$-divisor, and that there is a surjective morphism $f: X\to Z$ onto a normal variety $Z$ satisfying $K_X+B\sim _{\mathbb{Q}} f^*M$ for some big $\mathbb{Q}$-divisor $M$, and the augmented base locus ${\mathbf{B}}_+(M)$ does not contain the image of any log canonical centre of $(X,B)$. We will show that $(X,B)$ has a good log minimal model. An interesting special case is when $f$ is the identity morphism.
Level-raising and symmetric power functoriality, I
Authors: Clozel Laurent , Thorne Jack A. 
Published: March 2014

AbstractAs the simplest case of Langlands functoriality, one expects the existence of the symmetric power $S^n(\pi )$, where $\pi $ is an automorphic representation of ${\rm GL}(2,{\mathbb{A}})$ and ${\mathbb{A}}$ denotes the adeles of a number field $F$. This should be an automorphic representation of ${\rm GL}(N,{\mathbb{A}})$ ($N=n+1)$. This is known for $n=2,3$ and $4$. In this paper we show how to deduce the general case from a recent result of J.T. on deformation theory for ‘Schur representations’, combined with expected results on level-raising, as well as another case (a particular tensor product) of Langlands functoriality. Our methods assume $F$ totally real, and the initial representation $\pi $ of classical type.
On the homomorphisms between scalar generalized Verma modules
Authors: Matumoto Hisayosi 
Published: March 2014

AbstractIn this article, we study the homomorphisms between scalar generalized Verma modules. We conjecture that any homomorphism between scalar generalized Verma modules is a composition of elementary homomorphisms. The purpose of this article is to confirm the conjecture for some parabolic subalgebras under the assumption that the infinitesimal characters are regular.