bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryptic niche conservatism among evolutionary lineages of an invasive lizard
Authors: Schulte Ulrich , Hochkirch Axel , Lötters Stefan , Rödder Dennis , Schweiger Silke , Weimann Thomas , Veith Michael 
Published: April 2011

ABSTRACTAim There is increasing evidence that the quality and breadth of ecological niches vary among individuals, populations, evolutionary lineages and therefore also across the range of a species. Sufficient knowledge about niche divergence among clades might thus be crucial for predicting the invasion potential of species. We tested for the first time whether evolutionary lineages of an invasive species vary in their climate niches and invasive potential. Furthermore, we tested whether lineage‐specific models show a better performance than combined models.Location Europe.Methods We used species distribution models (SDMs) based on climatic information at native and invasive ranges to test for intra‐specific niche divergence among mitochondrial DNA (mtDNA) clades of the invasive wall lizardPodarcis muralis. Using DNA barcoding, we assigned 77 invasive populations in Central Europe to eight geographically distinct evolutionary lineages. Niche similarity among lineages was assessed and the predictive power of a combination of clade‐specific SDMs was compared with a combined SDM using the pooled records of all lineages.Results We recorded eight different invasive mtDNA clades in Central Europe. The analysed clades had rather similar realized niches in their native and invasive ranges, whereas inter‐clade niche differentiation was comparatively strong. However, we found only a weak correlation between geographic origin (i.e. mtDNA clade) and invasive occurrences. Clades with narrow realized niches still became successful invaders far outside their native range, most probably due to broader fundamental niches. The combined model using data for all invasive lineages achieved a much better prediction of the invasive potential.Conclusions Our results indicate that the observed niche differentiation among evolutionary lineages is mainly driven by niche realization and not by differences in the fundamental niches. Such cryptic niche conservatism might hamper the success of clade‐specific niche modelling. Cryptic niche conservatism may in general explain the invasion success of species in areas with apparently unsuitable climate.
The effect of cross‐listing on insider trading returns
Authors: Chang Millicent , Corbitt Ross 
Published: April 2011

AbstractHolding privileged positions within firms, insiders can acquire excessive private benefits based on their informational advantage. The bonding hypothesis suggests that this can be prevented when a firm is cross‐listed on an exchange with higher regulatory and legal costs compared with its home exchange. When cross‐listed insiders buy and sell shares, the returns earned are lower than in domestic firms. This difference is attributable to the increased shareholder protection in cross‐listed firms that constrains the extraction of private benefits, such that when cross‐listed insiders trade, they trade for non‐informational reasons.
Reasons patients give to use or not to use immunomodulating agents for multiple sclerosis
Authors: Visser L. H. , van der Zande A. 
Published: April 2011

Background:  Variations in the treatment of multiple sclerosis (MS) occur. This study was performed to obtain insight into the reasons why patients with MS use or do not use immunomodulating treatment (DMT).Methods:  We held a survey on the use of DMT in a group of 1572 patients with MS.Results:  Response rate was 89%. Of the patients, 31% were never on DMT, 21% had stopped DMT, 30% were still on the first DMT, and 18% had changed. The treatment‐naive patients were significantly older, had a longer duration of disease, and had a lower number of relapses per year (P < 0.0001). The most important reasons not to start the treatment of MS were the severity and phase of the disease (too mild or PP), possible side effects, the advice of the neurologist, and uncertainty about the effect of DMT. Fifteen percent of the patients stated that when choosing treatment, the information definitely had not been sufficient to make a proper choice. Reasons to stop or switch DMT were mainly side effects (primarily influenza‐like symptoms or injection site reactions), especially in RR‐MS, and the uncertainty of action or failure of DMT, especially in SP‐MS. According to the opinion of the patients, the neurologist had the most decisive role in starting or changing DMT, whilst the patient was primarily responsible in deciding to stop DMT.Conclusions:  Disease‐modifying therapy in MS is not well standardized in the Netherlands, because of the heterogeneous disease course and the variable doctors’ and patients’ expectations of the (side) effects of DMT.
Neuroglobin attenuates Alzheimer‐like tau hyperphosphorylation by activating Akt signaling
Authors: Chen Li‐Ming , Xiong Yan‐Si , Kong Fan‐Li , Qu Min , Wang Qun , Chen Xiao‐Qian , Wang Jian‐Zhi , Zhu Ling‐Qiang 
Published: April 2011

J. Neurochem. (2012) 120, 157–164.AbstractNeuroglobin (Ngb) is a recently identified member of hemoglobin family, distributed mainly in central and peripheral nervous systems. Recent studies suggest that Ngb can protect neural cells from β‐amyloid‐induced toxicity in Alzheimer disease (AD). Hyperphosphorylation of tau is another characterized pathological hallmark in the AD brains; however, it is not reported whether Ngb also affects tau phosphorylation. In this study, we found that the level of Ngb was significantly reduced in Tg2576 mice (a recognized mouse model of AD) and TgMAPt mice, and the level of Ngb was negatively correlated with tau phosphorylation. Over‐expression of Ngb attenuates tau hyperphosphorylation at multiple AD‐related sites induced by up‐regulation of glycogen synthase kinase‐3β (GSK‐3β), a crucial tau kinase. While Ngb activates Akt and thus inhibits GSK‐3β, simultaneously inhibition of Akt abolishes the effects of Ngb on GSK‐3β inhibition and tau hyperphosphorylation. Our data indicate that Ngb may attenuate tau hyperphosphorylation through activating Akt signaling pathway, implying a therapeutic target for AD.
The SLC36 family of proton‐coupled amino acid transporters and their potential role in drug transport
Authors: Thwaites David T , Anderson Catriona MH 
Published: April 2011

Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H+‐coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal protein breakdown. SLC36A1 has a relatively low affinity (Km 1–10 mM) for its substrates, which include zwitterionic amino and imino acids, heterocyclic amino acids and amino acid‐based drugs and derivatives used experimentally and/or clinically to treat epilepsy, schizophrenia, bacterial infections, hyperglycaemia and cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of glycine, proline and hydroxyproline. SLC36A2 also transports amino acid derivatives but has a narrower substrate selectivity and higher affinity (Km 0.1–0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the mRNA level and is a high‐affinity (Km 2–3 µM) transporter for proline and tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of amino acid‐based drugs by mediating transport in both the small intestine and kidney.LINKED ARTICLES This article is part of a themed section on Transporters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.164.issue‐7
NADPH oxidase (NOX) isoforms are inhibited by celastrol with a dual mode of action
Authors: Jaquet Vincent , Marcoux Julien , Forest Eric , Leidal Kevin G , McCormick Sally , Westermaier Yvonne , Perozzo Remo , Plastre Olivier , Fioraso‐Cartier Laetitia , Diebold Becky , Scapozza Leonardo , Nauseef William M , Fieschi Franck , Krause Karl‐Heinz , Bedard Karen 
Published: April 2011

BACKGROUND Celastrol is one of several bioactive compounds extracted from the medicinal plant Tripterygium wilfordii. Celastrol is used to treat inflammatory conditions, and shows benefits in models of neurodegenerative disease, cancer and arthritis, although its mechanism of action is incompletely understood.EXPERIMENTAL APPROACH Celastrol was tested on human NADPH oxidases (NOXs) using a panel of experiments: production of reactive oxygen species and oxygen consumption by NOX enzymes, xanthine oxidase activity, cell toxicity, phagocyte oxidase subunit translocation, and binding to cytosolic subunits of NOX enzymes. The effect of celastrol was compared with diphenyleneiodonium, an established inhibitor of flavoproteins.KEY RESULTS Low concentrations of celastrol completely inhibited NOX1, NOX2, NOX4 and NOX5 within minutes with concentration–response curves exhibiting higher Hill coefficients and lower IC50 values for NOX1 and NOX2 compared with NOX4 and NOX5, suggesting differences in their mode of action. In a cell‐free system, celastrol had an IC50 of 1.24 and 8.4 µM for NOX2 and NOX5, respectively. Cytotoxicity, oxidant scavenging, and inhibition of p47phox translocation could not account for NOX inhibition. Celastrol bound to a recombinant p47phox and disrupted the binding of the proline rich region of p22phox to the tandem SH3 domain of p47phox and NOXO1, the cytosolic subunits of NOX2 and NOX1, respectively.CONCLUSIONS AND IMPLICATIONS These results demonstrate that celastrol is a potent inhibitor of NOX enzymes in general with increased potency against NOX1 and NOX2. Furthermore, inhibition of NOX1 and NOX2 was mediated via a novel mode of action, namely inhibition of a functional association between cytosolic subunits and the membrane flavocytochrome.
SPA0355, a thiourea analogue, inhibits inflammatory responses and joint destruction in fibroblast‐like synoviocytes and mice with collagen‐induced arthritis
Authors: Lee YR , Hwang JK , Lee HS , Cheon YJ , Ryu JH , Lee SI , Kwak HB , Lee SM , Kim JS , Park JW , Jeon R , Park BH 
Published: April 2011

BACKGROUND AND PURPOSE NF‐κB has been implicated as a therapeutic target for the treatment of rheumatoid arthritis. We previously synthesized a thiourea analogue, SPA0355, which suppressed NF‐κB activity. Here we have assessed the anti‐inflammatory and anti‐arthritic effects of SPA0355.EXPERIMENTAL APPROACH We evaluated the effects of SPA0355 on human rheumatoid fibroblast‐like synoviocytes in vitro and on collagen‐induced arthritis (CIA) in mice in vivo.KEY RESULTS In vitro experiments demonstrated that SPA0355 suppressed chemokine production, matrix metalloproteinase secretion and cell proliferation induced by TNF‐α in rheumatoid fibroblast‐like synoviocytes. In addition, SPA0355 inhibited osteoclast differentiation induced by macrophage colony‐stimulating factor and the receptor activator of NF‐κB ligand, in bone marrow macrophages. Mice with CIA that were pretreated with SPA0355 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiological and histopathological findings, and inflammatory cytokine levels, than mice treated with vehicle. Mice treated with SPA0355, after the onset of CIA, also showed significantly decreased disease incidence and joint oedema. The in vitro and in vivo protective effects of SPA0355 were mediated by inhibition of the NF‐κB signalling pathway.CONCLUSION AND IMPLICATIONS Taken together, these results suggested that using SPA0355 to block the NF‐κB pathway in rheumatoid joints reduced both the inflammatory responses and tissue destruction. Therefore, SPA0355 may have therapeutic value in preventing or delaying joint destruction in patients with rheumatoid arthritis.
Inhibition of COX‐2 expression by endocannabinoid 2‐arachidonoylglycerol is mediated via PPAR‐γ
Authors: Du Huizhi , Chen Xiaolei , Zhang Jian , Chen Chu 
Published: April 2011

BACKGROUND AND PURPOSE Endocannabinoids have both anti‐inflammatory and neuroprotective properties against harmful stimuli. We previously demonstrated that the endocannabinoid 2‐arachidonoylglycerol (2‐AG) protects hippocampal neurons by limiting the inflammatory response via a CB1 receptor‐dependent MAPK/NF‐κB signalling pathway. The purpose of the present study was to determine whether PPARγ, an important nuclear receptor, mediates 2‐AG‐induced inhibition of NF‐κB phosphorylation and COX‐2 expression, and COX‐2‐enhanced miniature spontaneous excitatory postsynaptic currents (mEPSCs).EXPERIMENTAL APPROACH By using a whole‐cell patch clamp electrophysiological recording technique and immunoblot analysis, we determined mEPSCs, expression of COX‐2 and PPARγ, and phosphorylation of NF‐kB in mouse hippocampal neurons in culture.KEY RESULTS Exogenous and endogenous 2‐AG‐produced suppressions of NF‐κB‐p65 phosphorylation, COX‐2 expression and excitatory synaptic transmission in response to pro‐inflammatory interleukin‐1β (IL‐1β) and LPS were inhibited by GW9662, a selective PPARγ antagonist, in hippocampal neurons in culture. PPARγ agonists 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) and rosiglitazone mimicked the effects of 2‐AG on NF‐κB‐p65 phosphorylation, COX‐2 expression and mEPSCs, and these effects were eliminated by antagonism of PPARγ. Moreover, exogenous application of 2‐AG or elevation of endogenous 2‐AG by inhibiting its hydrolysis with URB602 or JZL184, selective inhibitors of monoacylglycerol lipase (MAGL), prevented the IL‐1β‐ and LPS‐induced reduction of PPARγ expression. The 2‐AG restoration of the reduced PPARγ expression was blocked or attenuated by pharmacological or genetic inhibition of the CB1 receptor.CONCLUSIONS AND IMPLICATIONS Our results suggest that CB1 receptor‐dependent PPARγ expression is an important and novel signalling pathway in endocannabinoid 2‐AG‐produced resolution of neuroinflammation in response to pro‐inflammatory insults.LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
QRS Fragmentation Is Not Associated with Poor Response to Cardiac Resynchronization Therapy
Authors: Rickard John , Zardkoohi Omeed , Popovic Zoran , Verhaert David , Sraow Dan , Baranowski Bryan , Martin David O. , Grimm Richard A. , Chung Mina K. , Tchou Patrick , Lindsay Bruce A. , Wilkoff Bruce L. 
Published: April 2011

Background: QRS fragmentation (fQRS) has been shown to be a marker of scar in patients with left ventricular dysfunction. Whether fQRS is associated with progressive left ventricular remodeling and increased mortality in patients receiving cardiac resynchronization therapy (CRT) is unclear. Methods: We reviewed the preimplant and follow‐up echocardiograms in 233 patients undergoing the new implantation of a CRT device between December 2001 and November 2006. Patients were included if they had a pre‐CRT ECG with appropriate filter settings (filter 0.16–100 or 0.16–150 Hz, 25 mm/s, 10 mm/mV), a left ventricular ejection fraction (LVEF) ≤40%, and New York Heart Association class II–IV symptoms on standard medical therapy. The 12‐lead electrocardiogram (ECG) was interpreted by two blinded reviewers for the presence of fQRS. Remodeling end points, including changes in LVEF and left ventricular end‐diastolic (LVEDV) and systolic (LVESV) volumes, were compared between patients with and without contiguous fQRS, and an assessment of all‐cause mortality was made. Results: Two hundred thirty‐two patients met inclusion criteria, of which 50 demonstrated fQRS in contiguous leads. There was no difference in improvement in LVEF (%) (7.9 ± 12.9 vs 6.8 ± 11.0, P = 0.60) or reduction in LVEDV (mL) (−30.1 ± 57.2 vs −15.7 ± 47.6) or LVESV (mL) (−33.7 ± 58.1 vs −22.7 ± 50.6, P = 0.40) between patients with and without contiguous fQRS. At a mean follow‐up of 4.4 ± 1.9 years, there were a total of 89 deaths, 22 (44.0%) in patients with contiguous fQRS and 67 (36.8%) without (log rank P = 0.31). Conclusions: QRS fragmentation is not a predictor of progressive ventricular remodeling or mortality in heart failure patients undergoing CRT. Ann Noninvasive Electrocardiol 2011;16(2):165–171
Epinephrine Bolus Test in Detecting Long QT Syndrome Mutation Carriers with Indeterminable Electrocardiographic Phenotype
Authors: Hekkala Anna‐Mari , Swan Heikki , Viitasalo Matti , Väänänen Heikki , Toivonen Lauri 
Published: April 2011

Background: In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval. Methods: Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 μg/kg bolus QT end, QT apex, and T‐wave peak‐to‐end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated. Results: Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2. Conclusions: Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype‐specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members. Ann Noninvasive Electrocardiol 2011;16(2):172–179
Use of Adenosine Test for the Exclusion of Preexcitation Syndrome in Asymptomatic Individuals
Authors: Grossman Alon , Wand Ori , Matezki Shlomi , Kerner Arthur , Assa Amit , Glikson Michael 
Published: April 2011

Background: Resting electrocardiogram is a routine procedure for the identification of potentially fatal conditions, including preexcitation syndrome (PES). Intravenous adenosine is a sensitive and specific means of exposing inapparent pathways in such patients. Yet, it may not be sensitive when complete atrioventricular (AV) block is not achieved because a low dose of adenosine is used. We evaluated the yield of a high‐dose adenosine test that achieved complete AV nodal block for unmasking inapparent pathway in a healthy population. Methods: We retrospectively reviewed all Israeli air force (IAF) academy candidates who were referred to adenosine test based on a cardiologist's suspicion of PES. The results of the adenosine test were recorded, including the adenosine dose required to achieve complete AV block. The medical records of the subjects were reviewed to identify any adverse cardiovascular outcome. Results: Fifty‐nine subjects who underwent adenosine test were followed for 35.42 ± 24 months. Complete AV block was achieved in all subjects with an average adenosine dose of 22.51 ± 12.67 mg. None of the subjects had evidence of an inapparent pathway. All subjects completed military service without adverse outcomes. Conclusions: The vast majority of young patients with a short PR interval do not have evidence of an accessory pathway and have a favorable prognosis. Thus, the yield of adenosine test in young combat recruits is questionable. Yet, if there is no evidence of an accessory pathway while achieving complete AV block on adenosine test, the chance of an accessory pathway being present is probably extremely low. Ann Noninvasive Electrocardiol 2011;16(2):180–183
Apoptosis, proliferation and Fas ligand expression in placental trophoblast from pregnancies complicated by HELLP syndrome or pre‐eclampsia
Authors: PRUSAC IVANA KUZMIC , ZEKIC TOMAS SANDRA , ROJE DAMIR 
Published: April 2011

AbstractObjective. To investigate apoptosis, proliferation and Fas ligand expression of placental trophoblast in the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and in pre‐eclampsia (PE), and to compare this with normal pregnancies. Design. Prospective study. Setting. University hospital in Croatia. Sample. Placentae from women with HELLP syndrome (n=10), PE (n=10) and normal pregnancies (n=10). Methods. The HELLP syndrome was diagnosed with platelets <100×109/L, aspartate aminotransferase (AST) and alanine transaminase (ALT) >70U/L and lactic acid dehydrogenase (LDH) > 600U/L. Pre‐eclampsia was diagnosed at blood pressure >140/90mmHg, with proteinuria >300mg/L/24hours. For detection of apoptosis and proliferation in villous trophoblast, antibodies M30 and Ki‐67 were used. Expression of Fas ligand was assessed using immunohistochemistry and the semiquantitative HSCORE method. Main Outcome Measures. Apoptosis, proliferation and Fas ligand expression in villous trophoblast. Results. Apoptosis, proliferation and Fas ligand expression were higher in villous trophoblast in HELLP syndrome than in the PE group (p=0.015, p=0.018 and p=0.002, respectively) and the control group (p=0.000, p=0.012 and p=0.049, respectively). Placentae from the PE group had higher levels of apoptosis (p=0.019), lower Fas ligand expression (p=0.029) and no difference in proliferation (p=0.887) compared with the control group. Conclusions. There is an increase in apoptosis, proliferation and Fas ligand expression in placentae from women with HELLP syndrome compared with placentae from PE and normal pregnancies. Our findings indicate the possibility of differential mechanisms behind HELLP syndrome and PE.
A Sagittarius-induced origin for the Monoceros ring
Authors: Michel-Dansac Léo , Abadi Mario G. , Navarro Julio F. , Steinmetz Matthias 
Published: April 2011

Abstract
The Monoceros ring is a collection of stars in nearly circular orbits at roughly 18 kpc from the Galactic Centre. It may have originated (i) as the response of the disc to perturbations excited by satellite companions or (ii) from the tidal debris of a disrupted dwarf galaxy. The metallicity of Monoceros stars differs from that of disc stars at comparable Galactocentric distances, an observation that disfavours the first scenario. On the other hand, circular orbits are difficult to accommodate in the tidal-disruption scenario, since it requires a satellite which at the time of disruption was itself in a nearly circular orbit. Such satellite could not have formed at the location of the ring and, given its low mass, dynamical friction is unlikely to have played a major role in its orbital evolution. We search cosmological simulations for low-mass satellites in nearly circular orbits and find that they result, almost invariably, from orbital changes induced by collisions with more massive satellites: the radius of the circular orbit thus traces the galactocentric distance of the collision. Interestingly, the Sagittarius dwarf, one of the most luminous satellites of the Milky Way, is in a polar orbit that crosses the Galactic plane at roughly the same Galactocentric distance as Monoceros. We use idealized simulations to demonstrate that an encounter with Sagittarius might well have led to the circularization and subsequent tidal demise of the progenitor of the Monoceros ring.